A novel homozygous splicing mutation in AK7 causes multiple morphological abnormalities of sperm flagella in patients from consanguineous Pakistani families  

作　　者：Ansar Hussain Huan Zhang Muhammad Zubair Wasim Shah Khalid Khan Imtiaz Ali Yousaf Raza Aurang Zeb Tanveer Abbas Nisar Ahmed Fazal Rahim Ghulam Mustafa Meftah Uddin Nadeem Ullah Musavir Abbas Muzammil Ahmad Khan Hui Ma Bo Yang Qing-Hua Shi 

机构地区：[1]Center for Reproduction and Genetics,First Affiliated Hospital of USTC,Hefei National Research Center for Physical Sciences at the Microscale,The CAS Key Laboratory of Innate Immunity and Chronic Disease,School of Basic Medical Sciences,Division of Life Sciences and Medicine,Biomedical Sciences and Health Laboratory of Anhui Province,Institute of Health and Medicine,Hefei Comprehensive National Science Center,University of Science and Technology of China,Hefei 230027,China [2]Gomal Centre of Biochemistry and Biotechnology,Gomal University,Dera Ismail Khan 29220,Pakistan

出　　处：《Asian Journal of Andrology》2025年第2期189-195,共7页亚洲男性学杂志(英文版)

基　　金：supported by the National Key Research and Development Program of China(No.2021YFC2700202,No.2022YFA0806303,and No.2022YFC2702601);the Global Select Project of the Institute of Health and Medicine,Hefei Comprehensive National Science Center(DJK-LX-2022010);the Joint Fund for New Medicine of USTC(YD9100002034).

摘　　要：Multiple morphological abnormalities of the flagella(MMAF)represent a severe form of sperm defects leading to asthenozoospermia and male infertility.In this study,we identified a novel homozygous splicing mutation(c.871-4 ACA>A)in the adenylate kinase 7(AK7)gene by whole-exome sequencing in infertile individuals.Spermatozoa from affected individuals exhibited typical MMAF characteristics,including coiled,bent,short,absent,and irregular flagella.Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella.Immunofluorescence staining confirmed the absence of AK7 protein from the patients’spermatozoa,validating the pathogenic nature of the mutation.This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans,expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.

关 键 词：AK7 ASTHENOZOOSPERMIA male infertility multiple morphological anomalies of the flagella 

分 类 号：R69[医药卫生—泌尿科学]