Health Management Center, Xiangya Hospital, Central South University, Changsha, People's Republic of China; School of Life Sciences, Central South University, Changsha, People's Republic of China.
School of Life Sciences, Central South University, Changsha, People's Republic of China; Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, People's Republic of China; Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, People's Republic of China.
Fertil Steril. 2020 Jan;113(1):158-166. doi: 10.1016/j.fertnstert.2019.08.069. Epub 2019 Nov 17.
To analyze the prevalence of FGFR1, FGF8, 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 FGFR1, FGF8, and FGF17 mutations.
Retrospective cohort.
University hospital.
PATIENT(S): A total of 145 IHH probands (125 men and 20 women) were recruited for this study.
INTERVENTIONS(S): Hormone assays.
MAIN OUTCOME MEASURE(S): Whole-exome sequencing, polymerase chain reaction-Sanger sequencing, in silico functional prediction.
RESULT(S): 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 FGFR1, FGF8, and FGF17 mutations.
CONCLUSION(S): We extended the mutational spectrum of FGFR1, FGF8, and FGF17 in IHH patients. The prevalence of FGFR1, FGF8, and FGF17 mutations in IHH was 12.4%. hCG/hMG therapy was effective to acquire fertility for patients with FGFR1, FGF8, and FGF17 mutations but has a risk of transmitting the mutations and IHH to the next generation.
分析中国特发性低促性腺激素性性腺功能减退症（IHH）患者 FGFR1、FGF8 和 FGF17 突变的流行情况，并分析 FGFR1、FGF8 和 FGF17 突变的 IHH 患者的临床表现和治疗结果。
回顾性队列研究。
大学医院。
共招募了 145 名 IHH 先证者（男 125 名，女 20 名）进行这项研究。
激素检测。
外显子组测序、聚合酶链反应-桑格测序、计算机功能预测。
在 18 名 IHH 患者中发现了 FGFR1 中的 6 个新突变（p.154_158del、p.E496Rfs*12、p.W190X、p.S134D、p.W10X 和 c.1552 + 3insT），FGF8 中的 2 个新突变（p.E176K 和 p.R184C），FGF17 中的 3 个新突变（p.48_52del、p.P120L 和 p.K191R），以及 FGFR1 中的 5 个已报道的突变（p.W289X、p.G237S、p.V102I、p.R250Q 和 p.T340M）。所有突变的功能后果均进行了计算机预测。除了促性腺激素性性腺功能减退症外，44.4%（8/18）的患者还存在其他临床畸形，包括牙缺失（3/18，16.7%）、听力损失（3/18，16.7%）和手部畸形（2/18，11.1%）。hCG/hMG 治疗可有效促进 FGFR1、FGF8 和 FGF17 突变的 IHH 患者的性发育。
我们扩展了 IHH 患者 FGFR1、FGF8 和 FGF17 的突变谱。FGFR1、FGF8 和 FGF17 突变在 IHH 中的患病率为 12.4%。hCG/hMG 治疗对 FGFR1、FGF8 和 FGF17 突变的患者获得生育能力有效，但存在将突变和 IHH 遗传给下一代的风险。
