A novel homozygous frameshift mutation in MNS1 associated with severe oligoasthenoteratozoospermia in humans  

作　　者：Yong Li Wei-Li Wang Chao-Feng Tu Lan-Lan Meng Tong-Yao Hu Juan Du Ge Lin Hong-Chuan Nie Yue-Qiu Tan 

机构地区：[1]Institute of Reproductive and Stem Cell Engineering,School of Basic Medical Science,Central South University,Changsha 410078,China [2]Reproductive and Genetic Hospital of CITIC-Xiangya,Changsha 410078,China [3]Clinical Research Center for Reproduction and Genetics in Hunan Province,Changsha 410078,China

出　　处：《Asian Journal of Andrology》2021年第2期197-204,共8页亚洲男性学杂志（英文版）

基　　金：This study was supported by grants from the National Key Science Program S&T Program(2018YFC1004900 to YQT);the National Natural Science Foundation of China(81971447 to YQT);the Science and Technology Major Project of the Ministry of Science and Technology of Hunan Province(2017SK1030 to YQT);Graduate Research and Innovation Projects of Central South University(2019zzts734 to YL and 2019zzts322 to WLW)。

摘　　要：Oligoasthenoteratozoospermia(OAT)refers to the combination of various sperm abnormalities,including a decreased sperm count,reduced motility,and abnormal sperm morphology.Only a few genetic causes have been shown to be associated with OAT.Herein,we identified a novel homozygous frameshift mutation in meiosis-specific nuclear structural 1(MNS1;NM_018365:c.603_604insG:p.Lys202Glufs*6)by whole-exome sequencing in an OAT proband from a consanguineous Chinese family.Subsequent variant screening identified four additional heterozygous MNS1 variants in 6/219 infertile individuals with oligoasthenospermia,but no MNS1 variants were observed among 223 fertile controls.Immunostaining analysis showed MNS1 to be normally located in the whole-sperm flagella,but was absent in the proband's sperm.Expression analysis by Western blot also confirmed that MNS1 was absent in the proband's sperm.Abnormal flagellum morphology and ultrastructural disturbances in outer doublet microtubules were observed in the proband's sperm.A total of three intracytoplasmic sperm injection cycles were carried out for the proband's wife,but they all failed to lead to a successful pregnancy.Overall,this is the first study to report a loss-of-function mutation in MNS1 causing OAT in a Han Chinese patient.

关 键 词：intracytoplasmic sperm injection male infertility meiosis-specific nuclear structural 1(MNS1) OLIGOASTHENOTERATOZOOSPERMIA whole-exome sequencing 

分 类 号：R698.2[医药卫生—泌尿科学]