Genotypic and phenotypic spectrum of CCDC141 variants in a Chinese cohort with congenital hypogonadotropic hypogonadism
Genotypic and phenotypic spectrum of CCDC141 variants in a Chinese cohort with congenital hypogonadotropic hypogonadism
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中国先天性低促性腺素性性腺功能减退症队列中 CCDC141 变异的基因型和表型谱
DOI：
10.1530/eje-19-1018
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发表时间：
2020-09-01
影响因子：
5.8
通讯作者：
Li, Jia-Da
中科院分区：
文献类型：
--
作者：
Hou, Qiao;Wu, Jiayu;Li, Jia-Da
目的：在一个大型中国先天性低促性腺激素性性腺功能减退症（CHH）队列中识别CCDC 141变异，并评估CCDC 141对CHH的贡献。设计图：方法：对177例CHH患者和450例中国汉族对照者进行全外显子组测序，并对12个CHH家系进行CCDC 141基因的多态性分析。其中4个变异体为私有突变;然而，在多名患者中鉴定出p.Q409X、p.Q871X和p.G1488S。高达75%（9/12）的患者在其他CHH相关基因中存在突变，这显著高于无CCDC 141 RSV的CHH患者。共分离分析表明，CCDC 141 RSV有75%（6/8）遗传自可育亲本。超过一半（58.3%，8/ 18）的患者表现出其他临床畸形，除了性腺功能减退症。一名患者窝藏CCDC 141 RSV显示逆转CHH后性类固醇replacement.Conclusions：我们的研究结果拓宽了CCDC 141在CHH的基因型谱，CCDC 141 RSV单独出现不足以导致CHH。CCDC 141 RSV患者的表型谱比最初认为的要宽得多。
Objective: To identify CCDC141 variants in a large Chinese cohort with congenital hypogonadot ropic hypogonadism (CHH) and to assess the contribution of CCDC141 to CHH. Design: Detailed phenotyping was conducted in CHH patients with CCDC141 variants and co-segregation analysis was performed, when possible.Methods: Whole-exome sequencing was performed in 177 CHH patients and 4 50 unrelated, ethnically matched controls from China.Results: Seven novel CCDC141 rare sequencing variants (RSVs) were identified in 12 CHH pedigrees. Four of the variants were private mutations; however, p.Q409X, p.Q871X and p.G1488S were identified in more than one patient. Up to 75% (9/12) of patients had mutations in other CHH-associated genes, which is significantly higher than CHH patients without CCDC141 RSVs. The co-segregation analysis for eight CHH families showed that 75% (6/8) CCDC141 RSVs were inherited from their fertile parents. Over half (58.3%, 8/ 18) of the patients exhibited other clinical deformities in addition to hypogonadism. One patient harbouring a CCDC141 RSV showed a reversal of CHH after sex-steroid replacement.Conclusions: Our results broaden the genotypic spectrum of CCDC141 in CHH, as CCDC141 RSVs alone do not appear sufficient to cause CHH. The phenotypic spectrum in patients with CCDC141 RSVs is much wider than originally believed.