原发性睫状体运动障碍
纤毛
生物
鞭毛
纤毛形成
运动纤毛
男性不育
复合杂合度
遗传学
轴丝
不育
基因
等位基因
支气管扩张
内科学
肺
医学
怀孕
作者
Tao Guo,Chaofeng Tu,Danhui Yang,Shuizi Ding,Lei Cheng,Rongchun Wang,Lv Liu,Kang Xi,Xiaomeng Shen,Yifeng Yang,Zhiping Tan,Yue‐Qiu Tan,Hong Luo
出处
期刊:Human Genetics
[Springer Nature]
日期:2021-01-03
卷期号:140 (5): 761-773
被引量:24
标识
DOI:10.1007/s00439-020-02241-4
摘要
Genetics-associated asthenoteratozoospermia is often seen in patients with multiple morphological abnormalities of the sperm flagella (MMAF). Although 24 causative genes have been identified, these explain only approximately half of patients with MMAF. Since sperm flagella and motile cilia (especially respiratory cilia) have similar axonemal structures, many patients with MMAF also exhibit respiratory symptoms, such as recurrent airway infection, chronic sinusitis, and bronchiectasis, which are frequently associated with primary ciliary dyskinesia (PCD), another recessive disorder. Here, exome sequencing was conducted to evaluate the genetic cause in 53 patients with MMAF and classic PCD/PCD-like symptoms. Two homozygous missense variants and a compound-heterozygous variant in the BRWD1 gene were identified in three unrelated individuals. BRWD1 staining was detected in the whole flagella and respiratory cilia of normal controls but was absent in BRWD1-mutated individuals. Transmission electron microscopy and immunostaining demonstrated that BRWD1 deficiency in human affected respiratory cilia and sperm flagella differently, as the absence of outer and inner dynein arms in sperm flagellum and respiratory cilia, while with a decreased number and outer doublet microtubule defects of respiratory cilia. To our knowledge, this is the first report of a BRWD1-variant-related disease in humans, manifesting as an autosomal recessive form of MMAF and PCD/PCD-like symptoms. Our data provide a basis for further exploring the molecular mechanism of BRWD1 gene during spermatogenesis and ciliogenesis.
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