Evidence map›Paper›PMID 25927242›Full record

ArticleThe Journal of clinical endocrinology and metabolism2015

46,XY Gonadal Dysgenesis due to a Homozygous Mutation in Desert Hedgehog (DHH) Identified by Exome Sequencing.

Ralf Werner, Hartmut Merz, Wiebke Birnbaum, Louise Marshall, Tatjana Schröder, Benedikt Reiz, Jennifer M Kavran, Tobias Bäumer, Philipp Capetian, Olaf Hiort

Open access · bronzeAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 73 citations in OpenAlex.

  1. Molecular Diagnosis of 46,XY Disorders of Sex Development: An Efficient Initial Molecular Analysis Using a Custom-Designed Targeted Gene Panel in a Single-Center Study.Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2026
    Article
  2. Article
  3. Review
  4. Review
  5. Classic genetic and hormonal switches during fetal sex development and beyond.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2023
    Article
  6. Review
  7. Article
  8. Article
  9. Article
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  11. Cilia signaling and obesity.Seminars in cell & developmental biology · 2021
    Review
  12. Dysgerminoma with a Somatic Exon 17Diagnostics (Basel, Switzerland) · 2020
    Article
  13. Article
  14. Male Hypogonadism and Disorders of Sex Development.Frontiers in endocrinology · 2020
    Review
  15. Molecular Characterization of XX Maleness.International journal of molecular sciences · 2019
    Review
  16. Article
  17. Article
  18. Hedgehog Signal and Genetic Disorders.Frontiers in genetics · 2019
    Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Ralf WernerDepartment of Paediatric and Adolescent Medicine, and Division of Experimental Paediatric Endocrinology and Diabetes (R.W., W.B., L.M., O.H.), Departments of Pathology (H.M.), Gynecology (T.S.), Neurology and Institute of Neurogenetics (P.C.), and Paediatric and Adult Movement Disorders and Neuropsychiatry and Institute of Neurogenetics (T.B.), Institute of Integrative and Experimental Genomics (B.R.), University of Luebeck, 23538 Luebeck, Germany; and Department of Biophysics and Biophysical Chemistry (J.M.K.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Hartmut MerzDepartment of Paediatric and Adolescent Medicine, and Division of Experimental Paediatric Endocrinology and Diabetes (R.W., W.B., L.M., O.H.), Departments of Pathology (H.M.), Gynecology (T.S.), Neurology and Institute of Neurogenetics (P.C.), and Paediatric and Adult Movement Disorders and Neuropsychiatry and Institute of Neurogenetics (T.B.), Institute of Integrative and Experimental Genomics (B.R.), University of Luebeck, 23538 Luebeck, Germany; and Department of Biophysics and Biophysical Chemistry (J.M.K.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Wiebke BirnbaumDepartment of Paediatric and Adolescent Medicine, and Division of Experimental Paediatric Endocrinology and Diabetes (R.W., W.B., L.M., O.H.), Departments of Pathology (H.M.), Gynecology (T.S.), Neurology and Institute of Neurogenetics (P.C.), and Paediatric and Adult Movement Disorders and Neuropsychiatry and Institute of Neurogenetics (T.B.), Institute of Integrative and Experimental Genomics (B.R.), University of Luebeck, 23538 Luebeck, Germany; and Department of Biophysics and Biophysical Chemistry (J.M.K.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Louise MarshallDepartment of Paediatric and Adolescent Medicine, and Division of Experimental Paediatric Endocrinology and Diabetes (R.W., W.B., L.M., O.H.), Departments of Pathology (H.M.), Gynecology (T.S.), Neurology and Institute of Neurogenetics (P.C.), and Paediatric and Adult Movement Disorders and Neuropsychiatry and Institute of Neurogenetics (T.B.), Institute of Integrative and Experimental Genomics (B.R.), University of Luebeck, 23538 Luebeck, Germany; and Department of Biophysics and Biophysical Chemistry (J.M.K.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Tatjana SchröderDepartment of Paediatric and Adolescent Medicine, and Division of Experimental Paediatric Endocrinology and Diabetes (R.W., W.B., L.M., O.H.), Departments of Pathology (H.M.), Gynecology (T.S.), Neurology and Institute of Neurogenetics (P.C.), and Paediatric and Adult Movement Disorders and Neuropsychiatry and Institute of Neurogenetics (T.B.), Institute of Integrative and Experimental Genomics (B.R.), University of Luebeck, 23538 Luebeck, Germany; and Department of Biophysics and Biophysical Chemistry (J.M.K.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Benedikt ReizDepartment of Paediatric and Adolescent Medicine, and Division of Experimental Paediatric Endocrinology and Diabetes (R.W., W.B., L.M., O.H.), Departments of Pathology (H.M.), Gynecology (T.S.), Neurology and Institute of Neurogenetics (P.C.), and Paediatric and Adult Movement Disorders and Neuropsychiatry and Institute of Neurogenetics (T.B.), Institute of Integrative and Experimental Genomics (B.R.), University of Luebeck, 23538 Luebeck, Germany; and Department of Biophysics and Biophysical Chemistry (J.M.K.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Jennifer M KavranDepartment of Paediatric and Adolescent Medicine, and Division of Experimental Paediatric Endocrinology and Diabetes (R.W., W.B., L.M., O.H.), Departments of Pathology (H.M.), Gynecology (T.S.), Neurology and Institute of Neurogenetics (P.C.), and Paediatric and Adult Movement Disorders and Neuropsychiatry and Institute of Neurogenetics (T.B.), Institute of Integrative and Experimental Genomics (B.R.), University of Luebeck, 23538 Luebeck, Germany; and Department of Biophysics and Biophysical Chemistry (J.M.K.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Tobias BäumerDepartment of Paediatric and Adolescent Medicine, and Division of Experimental Paediatric Endocrinology and Diabetes (R.W., W.B., L.M., O.H.), Departments of Pathology (H.M.), Gynecology (T.S.), Neurology and Institute of Neurogenetics (P.C.), and Paediatric and Adult Movement Disorders and Neuropsychiatry and Institute of Neurogenetics (T.B.), Institute of Integrative and Experimental Genomics (B.R.), University of Luebeck, 23538 Luebeck, Germany; and Department of Biophysics and Biophysical Chemistry (J.M.K.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Philipp CapetianDepartment of Paediatric and Adolescent Medicine, and Division of Experimental Paediatric Endocrinology and Diabetes (R.W., W.B., L.M., O.H.), Departments of Pathology (H.M.), Gynecology (T.S.), Neurology and Institute of Neurogenetics (P.C.), and Paediatric and Adult Movement Disorders and Neuropsychiatry and Institute of Neurogenetics (T.B.), Institute of Integrative and Experimental Genomics (B.R.), University of Luebeck, 23538 Luebeck, Germany; and Department of Biophysics and Biophysical Chemistry (J.M.K.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Olaf HiortDepartment of Paediatric and Adolescent Medicine, and Division of Experimental Paediatric Endocrinology and Diabetes (R.W., W.B., L.M., O.H.), Departments of Pathology (H.M.), Gynecology (T.S.), Neurology and Institute of Neurogenetics (P.C.), and Paediatric and Adult Movement Disorders and Neuropsychiatry and Institute of Neurogenetics (T.B.), Institute of Integrative and Experimental Genomics (B.R.), University of Luebeck, 23538 Luebeck, Germany; and Department of Biophysics and Biophysical Chemistry (J.M.K.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Institute for Integrative and Experimental Genomics · DEJohns Hopkins University · US

Funding

Structural and Biophysical Characterization of Hedgehog SignalingR01HD055545 · NICHD · JOHNS HOPKINS UNIVERSITY · PI LEAHY, DANIEL J · 2007 to 2015
$2.8M
NICHD NIH HHS R01 HD055545
6 · The paper itself

Abstract

background46,XY disorders of sex development (DSD) comprise a heterogeneous group of congenital conditions. Mutations in a variety of genes can affect gonadal development or androgen biosynthesis/action and thereby influence the development of the internal and external genital organs.

objectiveThe objective of the study was to identify the genetic cause in two 46,XY sisters of a consanguineous family with DSD and gonadal tumor formation.

methodsWe used a next-generation sequencing approach by exome sequencing. Electrophysiological and high-resolution ultrasound examination of peripheral nerves as well as histopathological examination of the gonads were performed.

resultsWe identified a novel homozygous R124Q mutation in the desert hedgehog gene (DHH), which alters a conserved residue among the three mammalian Hedgehog ligands sonic hedgehog, Indian hedgehog, and desert hedgehog. No other relevant mutations in DSD-related genes were encountered. The gonads of one patient showed partial gonadal dysgenesis with loss of Leydig cells in tubular areas with seminoma in situ and a hyperplasia of Leydig cell-like cells expressing CYP17A1 in more dysgenetic parts of the gonad. In addition, both patients suffer from a polyneuropathy. High-resolution ultrasound revealed a structural change of peripheral nerve structure that fits well to a minifascicle formation of peripheral nerves.

conclusionMutations in DHH play a role in 46,XY gonadal dysgenesis and are associated with seminoma formation and a neuropathy with minifascicle formation. Gonadal dysgenesis in these cases may be due to impairment of Sertoli cell-Leydig cell interaction during gonadal development.

Indexed as

HomozygoteMutationAdolescentAdultBase SequenceDNA Mutational AnalysisExomeFemaleGonadal Dysgenesis, 46,XYHedgehog ProteinsHigh-Throughput Nucleotide SequencingHumansMaleSeminomaSiblingsTesticular NeoplasmsDHH protein, humanHedgehog Proteins

Identifiers

PMID25927242
PMCPMC4490300
OpenAlexW2027876164

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.