ArticleThe Journal of clinical endocrinology and metabolism2016
Identification of an AR Mutation-Negative Class of Androgen Insensitivity by Determining Endogenous AR Activity.
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Article in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30citing papers in PubMed
6.4field-weighted citation impact, top 3% of its field
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Who cites it
30 citing papers in PubMed, 85 citations in OpenAlex.
- Current clinical care for women with complete androgen insensitivity syndrome across the European reference network on rare endocrine conditions.Journal of endocrinological investigation · 2026Article
- A novel androgen receptor gene splice site mutation induces aberrant mRNA splicing and internal in-frame deletion in androgen insensitivity syndrome.BMC medical genomics · 2026Article
- High-resolution functional mapping of androgen receptor variants.Nature biomedical engineering · 2026Article
- Case Report: Clinical and molecular genetic analysis of a patient with coexisting complete androgen insensitivity syndrome and neurofibromatosis type 1 and 15pstk + polymorphism.Frontiers in pediatrics · 2026Article
- Article
- The clinical diversity and molecular etiology in 46, XY disorders of sex development patients without uterus.Orphanet journal of rare diseases · 2025Article
- Complexities of complete androgen insensitivity syndrome: insights from a case report and literature review.The Journal of international medical research · 2024Review
- LINE1-mediated epigenetic repression of androgen receptor transcription causes androgen insensitivity syndrome.Scientific reports · 2024Article
- Classic genetic and hormonal switches during fetal sex development and beyond.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2023Article
- Genetic control of typical and atypical sex development.Nature reviews. Urology · 2023Review
- Article
- Molecular genetics and general management of androgen insensitivity syndrome.Intractable & rare diseases research · 2023Review
- Gene dosage changes in KCTD13 result in penile and testicular anomalies via diminished androgen receptor function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Differences of adrenal-derived androgens in 5α-reductase deficiency versus androgen insensitivity syndrome.Clinical and translational science · 2022Article
- Phenotypic and biochemical characteristics and molecular basis in 36 Chinese patients with androgen receptor variants.Orphanet journal of rare diseases · 2021Article
- The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome.International journal of molecular sciences · 2020Article
- Nonsense-associated altered splicing of MAP3K1 in two siblings with 46,XY disorders of sex development.Scientific reports · 2020Article
- Integrative and Analytical Review of the 5-Alpha-Reductase Type 2 Deficiency Worldwide.The application of clinical genetics · 2020Review
- Mobile DNA in Endocrinology: LINE-1 Retrotransposon Causing Partial Androgen Insensitivity Syndrome.The Journal of clinical endocrinology and metabolism · 2019Article
- The Role of International Databases in Understanding the Aetiology and Consequences of Differences/Disorders of Sex Development.International journal of molecular sciences · 2019Review
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Authors and funding
25 authors at 10 institutions in 5 countries.
N C HornigDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
M UkatDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
H U SchweikertDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
O HiortDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
R WernerDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
S L S DropDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
M CoolsDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
I A HughesDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
L AudiDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
S F AhmedDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
J DemiriDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
P RodensDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
L WorchDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
G WehnerDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
A E KulleDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
D DunstheimerDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
E Müller-RoßbergDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
T ReinehrDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
A T HadidiDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
A K EcksteinDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
C van der HorstDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
C SeifDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
R SiebertDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
O AmmerpohlDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
P-M HolterhusDepartment of Pediatrics (N.C.H., M.U., J.D., P.R., A.E.K., P.-M.H.), Division of Pediatric Endocrinology and Diabetes, and Institute of Human Genetics (L.W., R.S., O.A.), Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105 Kiel, Germany; Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Medicine III (H.U.S., G.W.), Institute for Biochemistry and Molecular Biology, Nussallee 11, 53115 Bonn, Germany; Department of Pediatrics (O.H., R.W.), Division of Experimental Pediatric Endocrinology, University of Luebeck, 23538 Luebeck, Germany; Department of Pediatrics (S.L.S.D.), Division of Pediatric Endocrinology, Sophia Childreńs Hospital, Erasmus Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; Department of Pediatric Endocrinology (Medical Center), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Pediatrics (I.A.H.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Pediatric Endocrinology Research Unit (L.A.), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Centro de Investigación Biomédica en Red Enfermedades Raras, Instituto de Salud Carlos III, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain; Developmental Endocrinology Research Group (S.F.A.), School of Medicine, University of Glasgow, Yorkhill Glasgow G3 8SJ, United Kingdom; Kinderklinik (D.D.), Klinikum Augsburg, 86156 Augsburg, Germany; Klinikum Esslingen (E.M.-R.), 73730 Esslingen, Germany; Department of Pediatrics (T.R.), Division of Pediatric Endocrinology, Diabetes, and Nutrition, University Witten/Herdecke, 45711 Datteln, Germany; Hypospadiezentrum (A.T.H.), 63500 Seligenstadt, Germany; Gemeinschaftspraxis für Kinderchirurgie (A.K.E.), 24119 Kronshagen, Germany; Urologische Gemeinschaftspraxis (C.v.d.H), and UROLOGIE Zentrum Kiel (C.S.), 24103 Kiel, Germany; and Institute of Human Genetics (R.S.), University of Ulm and University Hospital of Ulm, 89081 Ulm, Germany.
Kiel University · DEUniversity of Lübeck · DEUniversity Hospital Schleswig-Holstein · DEErasmus MC - Sophia Children’s Hospital · NLPraxis für Humangenetik · DEUniversity Hospital Ulm · DEUniversity of Bonn · DEUniversity of Cambridge · GBUniversity of Glasgow · GBWitten/Herdecke University · DE
Funding
Medical Research Council G1100236
Abstract
contextOnly approximately 85% of patients with a clinical diagnosis complete androgen insensitivity syndrome and less than 30% with partial androgen insensitivity syndrome can be explained by inactivating mutations in the androgen receptor (AR) gene.
objectiveThe objective of the study was to clarify this discrepancy by in vitro determination of AR transcriptional activity in individuals with disorders of sex development (DSD) and male controls.
designQuantification of DHT-dependent transcriptional induction of the AR target gene apolipoprotein D (APOD) in cultured genital fibroblasts (GFs) (APOD assay) and next-generation sequencing of the complete coding and noncoding AR locus.
settingThe study was conducted at a university hospital endocrine research laboratory. PATIENTS: GFs from 169 individuals were studied encompassing control males (n = 68), molecular defined DSD other than androgen insensitivity syndrome (AIS; n = 18), AR mutation-positive AIS (n = 37), and previously undiagnosed DSD including patients with a clinical suspicion of AIS (n = 46). INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE(S): DHT-dependent APOD expression in cultured GF and AR mutation status in 169 individuals was measured.
resultsThe APOD assay clearly separated control individuals (healthy males and molecular defined DSD patients other than AIS) from genetically proven AIS (cutoff < 2.3-fold APOD-induction; 100% sensitivity, 93.3% specificity, P < .0001). Of 46 DSD individuals with no AR mutation, 17 (37%) fell below the cutoff, indicating disrupted androgen signaling.
conclusionsAR mutation-positive AIS can be reliably identified by the APOD assay. Its combination with next-generation sequencing of the AR locus uncovered an AR mutation-negative, new class of androgen resistance, which we propose to name AIS type II. Our data support the existence of cellular components outside the AR affecting androgen signaling during sexual differentiation with high clinical relevance.
Indexed as
Apolipoproteins DAdultAndrogen-Insensitivity SyndromeBiological AssayCells, CulturedDisorders of Sex DevelopmentFibroblastsHigh-Throughput Nucleotide SequencingHumansMaleMutationReceptors, AndrogenSensitivity and SpecificityTestosteroneTranscription, GeneticAPOD protein, humanApolipoproteins DAR protein, humanboldenoneReceptors, AndrogenTestosterone
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