ArticleAmerican journal of human genetics2013
Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 134 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Molecular Basis of Inherited Reproductive Disorders
The Genetics of Neuroendocrine Reproductive Disorders and of the Cleft Lip and/or Palate
Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 264 citations in OpenAlex.
- Reversal of Congenital Hypogonadotropic Hypogonadism.The Journal of clinical endocrinology and metabolism · 2026Pooled it
- Genetics of Idiopathic Hypogonadotropic HypogonadismJournal of clinical research in pediatric endocrinology · 2026Review
- Sibling cases of congenital hypogonadotropic hypogonadism harboring compound heterozygousClinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2026Article
- FGF family in health and disease.Molecular biomedicine · 2026Review
- The intersection of disorders of sex development and cardiovascular diseases.Biology of sex differences · 2026Review
- Nanoplastics Impair GnRH Neuron Migration and Neuroendocrine Function: Emerging Players in the Pathogenesis of Reproductive Disorders.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Expanded Targeted-Exome Sequencing and Functional Validation Improve Molecular Diagnosis and Refine Genotype-Phenotype Correlations in Congenital Hypogonadotropic Hypogonadism.Neuroendocrinology · 2026Article
- Novel and recurrent genetic variants associated with male and female infertility.Journal of applied genetics · 2025Article
- The Lysine at Position 177 Is Essential to Limit the Inhibitory Capacities of Sprouty4 Protein in Normal and Cancer-Derived Cells.International journal of molecular sciences · 2025Article
- PROKR2 mutations and SPRY4 variants with uncertain significance in a Kallmann syndrome family: Incomplete penetrance.Global medical genetics · 2025Article
- Oligogenic analysis across broad phenotypes of 46,XY differences in sex development associated with NR5A1/SF-1 variants: findings from the international SF1next study.EBioMedicine · 2025Article
- Relationship between Pituitary Gland and Stem Cell in the Aspect of Hormone Production and Disease Prevention: A Narrative Review.Endocrine, metabolic & immune disorders drug targets · 2025Review
- Mini-Puberty, Physiological and Disordered: Consequences, and Potential for Therapeutic Replacement.Endocrine reviews · 2024Review
- Illuminating the terminal nerve: Uncovering the link between GnRH-1 neuron and olfactory development.The Journal of comparative neurology · 2024Article
- Clinical phenotype of a Kallmann syndrome patient with IL17RD and CPEB4 variants.Frontiers in endocrinology · 2024Review
- Prevalence of Deleterious Variants in MC3R in Patients With Constitutional Delay of Growth and Puberty.The Journal of clinical endocrinology and metabolism · 2023Article
- Variations in gender identity and sexual orientation of university students.Sexual medicine · 2023Article
- Clinical and molecular features of 40 Chinese patients with idiopathic hypogonadotropic hypogonadism.Translational andrology and urology · 2023Article
- Signal Transduction as an Assimilation of Signals with Different Origins and Different Intracellular States.International journal of molecular sciences · 2023Article
- A functional spectrum of PROKR2 mutations identified in isolated hypogonadotropic hypogonadism.Human molecular genetics · 2023Article
74 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 17 institutions in 10 countries.
Funding
Abstract
Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the >15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ~12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called "FGF8 synexpression" group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH.
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Registered trials
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.