中国人精子鞭毛多形态异常患者 DNAH1 基因突变谱：队列研究和文献复习。
Mutational landscape of DNAH1 in Chinese patients with multiple morphological abnormalities of the sperm flagella: cohort study and literature review.
机构信息
Department of Andrology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Department of Urology and Andrology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, China.
出版信息
J Assist Reprod Genet. 2021 Aug;38(8):2031-2038. doi: 10.1007/s10815-021-02201-5. Epub 2021 Apr 30.
PURPOSE
Multiple morphological abnormalities of the sperm flagella (MMAF) are important causes of male infertility. Mutations in DNAH1 are the main causative factors proven so far. We aim to determine the mutational landscape of DNAH1 in Chinese patients with MMAF.
METHODS
Forty-one Chinese patients with MMAF were enrolled and underwent a 10-gene next-generation sequencing panel screening.
RESULTS
Only the DNAH1 gene was found to have mutations in 12 of these unrelated individuals (29%). Combining published data from two other cohorts of Chinese men with MMAF, we suggest that p.P3909fs33, p.R868X, p.Q1518X, p.E3284K, and p.R4096L are hotspot mutations. A polymorphism-rs12163565 (G>A)- showed linkage to p.P3909fs33, suggesting that this involved a founder effect. Four of the 12 patients with DNAH1 mutations were able to use intracytoplasmic sperm injection with their partners and all were successful in obtaining embryos.
CONCLUSIONS
Hotspot mutations were identified for Chinese patients with MMAF. MMAF sub-phenotypes might be associated with different combinations of DNAH1 mutations.
目的
精子鞭毛多种形态异常（MMAF）是男性不育的重要原因。迄今为止，已证实 DNAH1 基因突变是主要的致病因素。本研究旨在确定中国 MMAF 患者中 DNAH1 的突变图谱。
方法
纳入 41 例 MMAF 中国患者，并进行了 10 基因下一代测序 panel 筛查。
结果
在这 12 名无血缘关系的个体中，仅在 DNAH1 基因中发现了突变（29%）。结合另外两个中国 MMAF 男性队列的已发表数据，我们提出 p.P3909fs33、p.R868X、p.Q1518X、p.E3284K 和 p.R4096L 是热点突变。多态性 rs12163565（G>A）与 p.P3909fs33 连锁，提示存在一个起源突变。在 12 例 DNAH1 突变患者中，有 4 例能够与伴侣进行胞浆内精子注射，且均成功获得胚胎。
结论
确定了中国 MMAF 患者的热点突变。MMAF 亚表型可能与 DNAH1 突变的不同组合有关。
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