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10.4103/aja202471
A novel homozygous splicing mutation in AK7 causes multiple morphological abnormalities of sperm flagella in patients from consanguineous Pakistani families
Hussain, Ansar1; Zhang, Huan1; Zubair, Muhammad1; Shah, Wasim1; Khan, Khalid1; Ali, Imtiaz1; Raza, Yousaf1; Zeb, Aurang1; Abbas, Tanveer1; Ahmed, Nisar1; Rahim, Fazal1; Mustafa, Ghulam1; Uddin, Meftah1; Ullah, Nadeem1; Abbas, Musavir1; Khan, Muzammil Ahmad2; Ma, Hui1; Yang, Bo1; Shi, Qing-Hua1
1Center 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
2Gomal Centre of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29220, Pakistan
Correspondence: Dr. B Yang (yangbo6674@163.com) or Dr. QH Shi (qshi@ustc.edu.cn)
Originally published: September 10, 2024 Received: April 7, 2024 Accepted: June 12, 2024
| Abstract |
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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.
Keywords: AK7; asthenozoospermia; male infertility; multiple morphological anomalies of the flagella
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