A novel homozygous splicing mutation in AK7 causes multiple morphological abnormalities of sperm flagella in patients from consanguineous Pakistani families
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.
Authors
- Qinghua Shi (ORCID: https://orcid.org/0000-0003-1180-9799)
- Muhammad Zubair (ORCID: https://orcid.org/0000-0002-8296-6452)
- Aurang Zeb (ORCID: https://orcid.org/0000-0002-2778-0444)
- Ghulam Mustafa (ORCID: https://orcid.org/0000-0001-5521-9921)
- Meftah Uddin
- Nadeem Ullah (ORCID: https://orcid.org/0000-0001-6089-8906)
- Wasim Shah
- Fazal Rahim (ORCID: https://orcid.org/0000-0002-5552-6443)
- Muzammil Ahmad Khan (ORCID: https://orcid.org/0000-0002-8686-2968)
- Tanveer Abbas (ORCID: https://orcid.org/0000-0002-1784-3077)
- Imtiaz Ali (ORCID: https://orcid.org/0000-0002-2170-6841)
- Huan Zhang (ORCID: https://orcid.org/0000-0002-3968-6463)
- Hui Ma (ORCID: https://orcid.org/0000-0002-0995-2345)
- Nisar Ahmed (ORCID: https://orcid.org/0009-0002-9296-8512)
- Khalid Khan (ORCID: https://orcid.org/0000-0001-5639-0704)
- Musavir Abbas
- Yousaf Raza
- Ansar Hussain
- Bo Yang (ORCID: https://orcid.org/0000-0001-5586-3186)
Institutions
- University of Science and Technology of China (CN)
- Gomal University (PK)
Publication Details
- Journal
- Asian Journal of Andrology
- Published
- 2024-09-10
- DOI
- https://doi.org/10.4103/aja202471
- Citations
- 4
- Primary Topic
- Sperm and Testicular Function
- Type
- article
- Field-Weighted Citation Impact
- 2.15
Funders
- Zhejiang University
- University of Science and Technology of China
- National Key Research and Development Program of China