A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms.
A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms.
复制标题
CCDC103中复发性的纯合错义突变会导致小气动蛋白酶植物，这是由于混乱的动力蛋白臂而导致的。
DOI：
10.4103/aja2021122
复制
发表时间：
2022-05
影响因子：
2.9
通讯作者：
中科院分区：
文献类型：
--
作者：
弱畸形精子症是最严重的精子质量缺陷类型之一。大多数病例是由于编码精子鞭毛成分的基因突变造成的，精子鞭毛具有与运动纤毛相似的超微结构。卷曲螺旋结构域103（CCDC103）是一种外动力蛋白臂组装因子，CCDC103的致病性变体引起原发性纤毛运动障碍（PCD）。然而，CCDC103致病变异体是否会导致严重的弱畸形精子症还有待确定。全外显子组测序（WES）进行了两个人的非综合征弱畸形精子症的近亲家庭。鉴定了分离具有不育表型的再育的纯合CCDC 103变体（ENST 00000035776.2，c.461A>C，p.His154Pro）。CCDC103 p.His154Pro以前被报道为导致PCD的高流行率突变，尽管这些PCD个体的生殖表型是未知的。透射电子显微镜（TEM）显示，受影响的个人的精子中段严重受损与紊乱的动力蛋白臂，类似的异常超微结构的呼吸纤毛的PCD个人具有相同的突变。因此，我们的研究结果扩大了CCDC103 p.His154Pro作为一种新的非综合征性弱精子症致病基因的表型谱。
Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals’ spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.