Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran.
Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran.
Gene. 2019 May 30;699:16-23. doi: 10.1016/j.gene.2019.02.060. Epub 2019 Mar 5.
Asthenozoospermia (ASZ) is a condition characterized by reduced sperm motility in semen affecting approximately 19% of infertile men. Major risk factors, particularly gene mutations, still remain unknown. The main aim of the present study was to identify novel genes and mutations that may influence human sperm motility.
Whole-exome sequencing (WES) was performed on a large pedigree of infertile men (n = 5) followed by bioinformatics analyses. Candidate pathogenic variants were screened in a control cohort of 400 ancestry-matched Iranian fertile men, 30 unrelated men with idiopathic ASZ, and public databases.
A rare mutation in GFPT2 gene (c.1097G > A; p.Arg366Gln) located in the SIS 1 domain was segregated with the phenotype and was consistent with autosomal recessive inheritance. The in silico analyses revealed that the mutation might affect the function of SIS 1 domain and abolish its carbohydrate-binding ability.
Homozygosity of the GFPT2 p.Arg366Gln mutation was associated with increased levels of reactive oxygen species (ROS) in spermatozoa and decreased sperm motility.
弱精症（ASZ）是一种精液中精子运动能力降低的病症，影响约 19%的不育男性。主要的风险因素，特别是基因突变，仍然未知。本研究的主要目的是确定可能影响人类精子运动能力的新基因和突变。
对一个大型不育男性家系（n=5）进行全外显子组测序（WES），然后进行生物信息学分析。在 400 名具有伊朗亲缘关系的生育能力正常的男性、30 名非相关的特发性 ASZ 男性和公共数据库中筛选候选致病性变异。
在 SIS 1 结构域中发现了一个位于 GFPT2 基因（c.1097G>A；p.Arg366Gln）的罕见突变，与表型分离且符合常染色体隐性遗传。计算机分析表明，该突变可能影响 SIS 1 结构域的功能并使其丧失碳水化合物结合能力。
GFPT2 p.Arg366Gln 突变的纯合子与精子中活性氧（ROS）水平升高和精子运动能力降低有关。
