一个新的 AK7 基因纯合错义突变导致了鞭毛的多种形态异常和少精子症。
A novel homozygous missense mutation in AK7 causes multiple morphological anomalies of the flagella and oligoasthenoteratozoospermia.
机构信息
Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
NHC Key Laboratory of Study On Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, 230032, Anhui, China.
出版信息
J Assist Reprod Genet. 2022 Jan;39(1):261-266. doi: 10.1007/s10815-021-02363-2. Epub 2021 Dec 2.
Abstract
PURPOSE
To identify the genetic causes of multiple morphological anomalies of the flagella (MMAF) and oligoasthenoteratozoospermia (OAT).
METHODS
Whole-exome sequencing (WES) was performed on the proband to identify pathogenic mutation for infertility. Western blotting and immunofluorescence analysis detected the expression level and localization of adenylate kinase 7 (AK7).
RESULTS
We identified a novel homozygous missense mutation (NM_152327: c.1846G > A; p.E616K) in AK7 in two brothers with MMAF and OAT from a consanguineous family by WES. Western blotting and immunofluorescence experiments determined that the expression level of AK7 decreased in the sperm from the proband. The proband and his wife underwent two cycles of intracytoplasmic sperm injection (ICSI) treatment but got unfavorable outcomes.
CONCLUSION
This study could provide precise genetic diagnosis for the patient and expand the spectrum of AK7 mutations.
摘要
目的
鉴定多发性鞭毛形态异常（MMAF）和少精弱精症（OAT）的遗传原因。
方法
对先证者进行全外显子组测序（WES），以鉴定不育的致病性突变。Western blot 和免疫荧光分析检测腺嘌呤激酶 7（AK7）的表达水平和定位。
结果
我们通过 WES 在一个有血缘关系的家庭中发现了两名患有 MMAF 和 OAT 的兄弟携带 AK7 的新型纯合错义突变（NM_152327：c.1846G > A；p.E616K）。Western blot 和免疫荧光实验确定先证者精子中的 AK7 表达水平降低。先证者和他的妻子接受了两次胞浆内精子注射（ICSI）治疗，但结果不佳。
结论
本研究可为患者提供精确的基因诊断，并扩展 AK7 突变谱。
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