ArticleThe Journal of clinical endocrinology and metabolism2010
Nonsense mutations in FGF8 gene causing different degrees of human gonadotropin-releasing deficiency.
Article in The Journal of clinical endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.
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.
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Who cites it
36 citing papers in PubMed, 79 citations in OpenAlex.
- Genetics of Idiopathic Hypogonadotropic HypogonadismJournal of clinical research in pediatric endocrinology · 2026Review
- Fibroblast growth factor 8: Multifaceted role in development and developmental disorder.Genes & diseases · 2025Review
- Heterozygous deletion of 10q24.31-q24.33- a new syndrome associated with multiple congenital anomalies: case report and literature review.Neurological research and practice · 2025Article
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- [Research Progress of Fibroblast Growth Factor 8's Role in the Regulation of Bone Development and Homeostasis].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022Review
- Genetic architecture of self-limited delayed puberty and congenital hypogonadotropic hypogonadism.Frontiers in endocrinology · 2022Review
- Pituitary Gonadotropin Gene Expression During Induced Onset of Postsmolt Maturation in Male Atlantic Salmon:Frontiers in endocrinology · 2022Article
- Mechanisms of Central Hypogonadism.International journal of molecular sciences · 2021Review
- Article
- Genetic Evaluation of Patients With Delayed Puberty and Congenital Hypogonadotropic Hypogonadism: Is it Worthy of Consideration?Frontiers in endocrinology · 2020Review
- GnRH-1 Neural Migration From the Nose to the Brain Is Independent From Slit2, Robo3 and NELL2 Signaling.Frontiers in cellular neuroscience · 2019Article
- Loss-of-function mutations in FGF8 can be independent risk factors for holoprosencephaly.Human molecular genetics · 2018Article
- Homozygous nonsense mutation Trp28X in the LHB gene causes male hypogonadism.Journal of assisted reproduction and genetics · 2018Article
- Genetic, environmental, and epigenetic factors involved in CAKUT.Nature reviews. Nephrology · 2015Review
- Fibroblast growth factor receptor signaling in hereditary and neoplastic disease: biologic and clinical implications.Cancer metastasis reviews · 2015Review
- Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment.Nature reviews. Endocrinology · 2015Review
- Point mutations in KAL1 and the mitochondrial gene MT-tRNA(cys) synergize to produce Kallmann syndrome phenotype.Scientific reports · 2015Article
- Fgf8-Deficient Mice Compensate for Reduced GnRH Neuronal Population and Exhibit Normal Testicular Function.Frontiers in endocrinology · 2015Article
- GnRH, anosmia and hypogonadotropic hypogonadism--where are we?Frontiers in neuroendocrinology · 2015Review
- Role of gonadotropin-releasing hormone receptor mutations in patients with a wide spectrum of pubertal delay.Fertility and sterility · 2014Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
contextFGFR1 mutations cause isolated hypogonadotropic hypogonadism (IHH) with or without olfactory abnormalities, Kallmann syndrome, and normosmic IHH respectively. Recently, missense mutations in FGF8, a key ligand for fibroblast growth factor receptor (FGFR) 1 in the ontogenesis of GnRH, were identified in IHH patients, thus establishing FGF8 as a novel locus for human GnRH deficiency.
objectiveOur objective was to analyze the clinical, hormonal, and molecular findings of two familial IHH patients due to FGF8 gene mutations. METHODS AND PATIENTS: The entire coding region of the FGF8 gene was amplified and sequenced in two well-phenotyped IHH probands and their relatives.
resultsTwo unique heterozygous nonsense mutations in FGF8 (p.R127X and p.R129X) were identified in two unrelated IHH probands, which were absent in 150 control individuals. These two mutations, mapped to the core domain of FGF8, impact all four human FGF8 isoforms, and lead to the deletion of a large portion of the protein, generating nonfunctional FGF8 ligands. The p.R127X mutation was identified in an 18-yr-old Kallmann syndrome female. Her four affected siblings with normosmic IHH or delayed puberty also carried the p.R127X mutation. Additional developmental anomalies, including cleft lip and palate and neurosensorial deafness, were also present in this family. The p.R129X mutation was identified in a 30-yr-old man with familial normosmic IHH and severe GnRH deficiency.
conclusionsWe identified the first nonsense mutations in the FGF8 gene in familial IHH with variable degrees of GnRH deficiency and olfactory phenotypes, confirming that loss-of-function mutations in FGF8 cause human GnRH deficiency.
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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.