Genotypic and phenotypic spectra of FGFR1, FGF8, and FGF17 mutations in a Chinese cohort with idiopathic hypogonadotropic hypogonadism

FGFR1, FGF8, and FGF17 mutations occurred in 12.4% of patients with IHH, frequently with hand malformation, dental agenesis, and hearing loss. Men with FGFR1 mutations were more likely to have IHH than women.

Volume 113, Issue 1, Pages 158–166


Meichao Men, M.D., Jiayu Wu, M.S., Yaguang Zhao, M.S., Xiaoliang Xing, Ph.D., Fang Jiang, M.D., Ruizhi Zheng, M.D., Jia-Da Li, Ph.D.



To analyze the prevalence of FGFR1FGF8, and FGF17 mutations in a Chinese cohort with idiopathic hypogonadotropic hypogonadism (IHH) and to characterize the clinical presentations and therapeutic outcomes of IHH patients with FGFR1FGF8, and FGF17 mutations.


Retrospective cohort.


University hospital.


A total of 145 IHH probands (125 men and 20 women) were recruited for this study.


Hormone assays.

Main Outcome Measure(s)

Whole-exome sequencing, polymerase chain reaction–Sanger sequencing, in silico functional prediction.


Six novel mutations (p.154_158del, p.E496Rfs*12, p.W190X, p.S134D, p.W10X, and c.1552 + 3insT) in FGFR1, two novel mutations (p.E176K and p.R184C) in FGF8, three novel mutations (p.48_52del, p.P120L, and p.K191R) in FGF17, and five reported mutations (p.W289X, p.G237S, p.V102I, p.R250Q, and p.T340M) in FGFR1 were identified in 18 IHH patients. The functional consequences of all mutations were analyzed in silico. In addition to hypogonadotropic hypogonadism, 44.4% (8/18) patients exhibited other clinical deformities, including dental agenesis (3/18, 16.7%), hearing loss (3/18, 16.7%), and hand malformation (2/18, 11.1%). hCG/hMG therapy was effective in promoting sexual development in IHH patients with FGFR1FGF8, and FGF17 mutations.


We extended the mutational spectrum of FGFR1FGF8, and FGF17 in IHH patients. The prevalence of FGFR1FGF8, and FGF17 mutations in IHH was 12.4%. hCG/hMG therapy was effective to acquire fertility for patients with FGFR1FGF8, and FGF17 mutations but has a risk of transmitting the mutations and IHH to the next generation.

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