Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families  

作　　者：Ihsan Khan Basit Shah Sobia Dil Nadeem Ullah Jian-Teng Zhou Da-Ren Zhao Yuan-Wei Zhang Xiao-Hua Jiang Ranjha Khan Asad Khan Haider Ali Muhammad Zubair Wasim Shah Huan Zhang Qing-Hua Shi 

机构地区：[1]First Affiliated Hospital of USTC,Hefei National Laboratory for Physical Sciences at Microscale,the CAS Key Laboratory of Innate Immunity and Chronic Disease,School of Basic Medical Sciences,Division of Life Sciences and Medicine,CAS Center for Excellence in Molecular Cell Science,Collaborative Innovation Center of Genetics and Development,University of Science and Technology of China,Hefei 230027,China

出　　处：《Asian Journal of Andrology》2021年第6期627-632,共6页亚洲男性学杂志（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.32070850);the National Natural Science Foundation of China(No.31630050,31890780,and 32061143006);the National Key Research and Developmental Program of China(2018YFC1003900,2019YFA0802600,and 2016YFC1000600);the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB19000000);the Fundamental Research Funds for the Central Universities(No.YD2070002006).

摘　　要：Multiple morphological abnormalities of the sperm flagella(MMAF)is a specific type of asthenoteratozoospermia,presenting with multiple morphological anomalies in spermatozoa,such as absent,bent,coiled,short,or irregular caliber flagella.Previous genetic studies revealed pathogenic mutations in genes encoding cilia and flagella-associated proteins(CFAPs;e.g.,CFAP43,CFAP44,CFAP65,CFAP69,CFAP70,and CFAP251)responsible for the MMAF phenotype in infertile men from different ethnic groups.However,none of them have been identified in infertile Pakistani males with MMAF.In the current study,two Pakistani families with MMAF patients were recruited.Whole-exome sequencing(WES)of patients and their parents was performed.WES analysis reflected novel biallelic loss-of-function mutations in CFAP43 in both families(Family 1:ENST00000357060.3,p.Arg300Lysfs*22 and p.Thr526Serfs*43 in a compound heterozygous state;Family 2:ENST00000357060.3,p.Thr526Serfs*43 in a homozygous state).Sanger sequencing further confirmed that these mutations were segregated recessively in the families with the MMAF phenotype.Semiquantitative reverse-transcriptase polymerase chain reaction(qRT-PCR)was carried out to detect the effect of the mutation on mRNA of the affected gene.Previous research demonstrated that biallelic loss-of-function mutations in CFAP43 accounted for the majority of all CFAP43-mutant MMAF patients.To the best of our knowledge,this is the first study to report CFAP43 biallelic loss-of-function mutations in a Pakistani population with the MMAF phenotype.This study will help researchers and clinicians to understand the genetic etiology of MMAF better.

关 键 词：cilia and flagella-associated proteins male infertility multiple morphological abnormalities of the sperm flagella whole-exome sequencing 

分 类 号：R698.2[医药卫生—泌尿科学]