An M1AP homozygous splice-site mutation associated with severe oligozoospermia in a consanguineous family
An M1AP homozygous splice-site mutation associated with severe oligozoospermia in a consanguineous family
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M1AP纯合剪接位点突变与近亲结婚严重少精症相关
DOI：
10.1111/cge.13712
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发表时间：
2020
影响因子：
3.5
通讯作者：
Du Juan
中科院分区：
文献类型：
--
作者：
Tu Chaofeng;Wang Ying;Nie Hongchuan;Meng Lanlan;Wang Weili;Li Yong;Li Dongyan;Zhang Huan;Lu Guangxiu;Lin Ge;Tan Yue-Qiu;Du Juan
严重少精症（SO）是男性不育的重要原因。其病因和发病机制与遗传异常有关；然而，大多数特发性人类SO的遗传原因仍不清楚。在这里，我们报告了一个纯合剪接位点突变m1ap（减数分裂1相关蛋白；NM_138804, c.1435‐1G> a）在一个来自近亲汉族家庭的SO患者中观察到。他的父母和有生育能力的兄弟是杂合突变。剪接变异导致患者精子中缺乏M1AP蛋白。患者精子的超微结构和免疫染色分析显示线粒体鞘高度异常肿胀，轴索结构正常。随后的突变筛选在4/243例特发性SO患者中发现了3个额外的杂合sm1ap变异体，但在223例可育者中发现了nom1ap变异体。此外，先前的一项研究报道，m1ap敲除小鼠由于减数分裂停滞而表现出SO。因此，我们的研究结果表明，m1apmutation可能代表了导致人类SO的新的基因改变。
Severe oligozoospermia (SO) is an important cause of male infertility. Its etiology and pathogenesis are associated with genetic abnormalities; however, the genetic causes of the majority of idiopathic human SO remain unclear. Here, we report a homozygous splice‐site mutation inM1AP(meiosis 1 associated protein; NM_138804, c.1435‐1G>A) observed in a patient with SO from a consanguineous Han Chinese family. His parents and fertile brother were heterozygous for the mutation. The splice variant led to a lack of M1AP protein in the patient's spermatozoa. Ultrastructural and immunostaining analyses of patient's spermatozoa showed highly aberrant swollen mitochondrial sheaths with normal axonemal structures. Subsequent mutation screening identified three additional heterozygousM1APvariants in 4/243 subjects with idiopathic SO, but noM1APvariants among 223 fertile subjects. Additionally, a previously study reported thatM1apknock‐out mice exhibited SO due to meiotic arrest. Hence, our findings indicate thatM1APmutation might represent novel genetic alteration responsible for human SO.