ArticleEndocrine connections2015
FGFR1 and PROKR2 rare variants found in patients with combined pituitary hormone deficiencies.
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Article in Endocrine connections, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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20citing papers in PubMed, 1 pooled it
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Pooled it
- Pleiotropic genes linking congenital hypogonadotropic hypogonadism and cleft lip/palate: evidence from a genomic CHH cohort study.European journal of human genetics : EJHG · 2026Article
- Exploring the mediating role of potential therapeutic genes in the pathogenesis of hypopituitarism through the metabolites from a genomic perspective.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Diagnostic Challenges of Short Stature and Growth Hormone Insufficiency Across Different Genetic Etiologies.Biomedicines · 2025Review
- Involvement of a Novel Variant ofInternational journal of molecular sciences · 2025Article
- Trio-based whole exome sequencing in patients with ectopic posterior pituitary.Frontiers in pediatrics · 2024Article
- Article
- Combined pituitary hormone deficiency in a patient with anClinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2022Article
- Advances in differential diagnosis and management of growth hormone deficiency in children.Nature reviews. Endocrinology · 2021Review
- Comprehensive Identification of Pathogenic Gene Variants in Patients With Neuroendocrine Disorders.The Journal of clinical endocrinology and metabolism · 2021Article
- Article
- Genomics and Epigenomics of Pituitary Tumors: What Do Pathologists Need to Know?Endocrine pathology · 2021Review
- Congenital Hypopituitarism During the Neonatal Period: Epidemiology, Pathogenesis, Therapeutic Options, and Outcome.Frontiers in pediatrics · 2020Review
- Sexually dimorphic distribution of Prokr2 neurons revealed by the Prokr2-Cre mouse model.Brain structure & function · 2017Article
- Digenic Inheritance of PROKR2 and WDR11 Mutations in Pituitary Stalk Interruption Syndrome.The Journal of clinical endocrinology and metabolism · 2017Review
- ANOS1: a unified nomenclature for Kallmann syndrome 1 gene (KAL1) and anosmin-1.Briefings in functional genomics · 2017Article
- Targeted sequencing in FGF/FGFR genes and association analysis of variants for mandibular prognathism.Medicine · 2017Observational
- Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era.Endocrine reviews · 2016Review
- PITUITARY STALK INTERRUPTION SYNDROME: REPORT OF TWO CASES AND LITERATURE REVIEW.Acta endocrinologica (Bucharest, Romania : 2005)Article
- Update on new GH-IGF axis genetic defects.Archives of endocrinology and metabolismReview
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Authors and funding
17 authors at 1 institution in 1 country.
Fernanda A CorreaUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA fernandacorrea@usp.br.
Ericka B TrarbachUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Cintia TussetUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Ana Claudia LatronicoUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Luciana R MontenegroUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Luciani R CarvalhoUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Marcela M FrancaUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Aline P OttoUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Everlayny F CostalongaUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Vinicius N BritoUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Ana Paula AbreuUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Mirian Y NishiUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Alexander A L JorgeUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Ivo J P ArnholdUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Yisrael SidisUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Nelly PitteloudUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Berenice B MendoncaUnidade de Endocrinologia do DesenvolvimentoLaboratório de Hormônios e Genética Molecular LIM42Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular LIM25, Hospital das Clínicas, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 255, 05403-000 São Paulo, BrazilCentre Hospitalier Universitaire Vaudois (CHUV)Faculté de Biologie et Médecine de l'Univesité de Lausanne, Lausanne, SwitzerlandDivision of EndocrinologyDiabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Brigham and Women's Hospital · US
Funding
No grant is acknowledged in the PubMed record.
Abstract
The genetic aetiology of congenital hypopituitarism (CH) is not entirely elucidated. FGFR1 and PROKR2 loss-of-function mutations are classically involved in hypogonadotrophic hypogonadism (HH), however, due to the clinical and genetic overlap of HH and CH; these genes may also be involved in the pathogenesis of CH. Using a candidate gene approach, we screened 156 Brazilian patients with combined pituitary hormone deficiencies (CPHD) for loss-of-function mutations in FGFR1 and PROKR2. We identified three FGFR1 variants (p.Arg448Trp, p.Ser107Leu and p.Pro772Ser) in four unrelated patients (two males) and two PROKR2 variants (p.Arg85Cys and p.Arg248Glu) in two unrelated female patients. Five of the six patients harbouring the variants had a first-degree relative that was an unaffected carrier of it. Results of functional studies indicated that the new FGFR1 variant p.Arg448Trp is a loss-of-function variant, while p.Ser107Leu and p.Pro772Ser present signalling activity similar to the wild-type form. Regarding PROKR2 variants, results from previous functional studies indicated that p.Arg85Cys moderately compromises receptor signalling through both MAPK and Ca(2) (+) pathways while p.Arg248Glu decreases calcium mobilization but has normal MAPK activity. The presence of loss-of-function variants of FGFR1 and PROKR2 in our patients with CPHD is indicative of an adjuvant and/or modifier effect of these rare variants on the phenotype. The presence of the same variants in unaffected relatives implies that they cannot solely cause the phenotype. Other associated genetic and/or environmental modifiers may play a role in the aetiology of this condition.
Indexed as
combined pituitary hormone deficienciesFGFR1hypopituitarismPROKR2
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