1.A novel homozygous splicing mutation in AK7 causes multiple morphological abnormalities of sperm flagella in patients from consanguineous Pakistani families.
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
Asian Journal of Andrology 2025;27(2):189-195
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.
Humans
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Male
;
Sperm Tail/ultrastructure*
;
Homozygote
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Consanguinity
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Asthenozoospermia/pathology*
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Infertility, Male/genetics*
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Mutation
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Pakistan
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Adenylate Kinase/genetics*
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Adult
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Pedigree
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RNA Splicing
;
Exome Sequencing
;
Spermatozoa
Result Analysis
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