A novel homozygous frameshift variant in DNAH8 causes multiple morphological abnormalities of the sperm flagella in a consanguineous Pakistani family.
- Author:
Sobia DIL
1
;
Asad KHAN
1
;
Ahsanullah UNAR
1
;
Meng-Lei YANG
1
;
Imtiaz ALI
1
;
Aurang ZEB
1
;
Huan ZHANG
1
;
Jian-Teng ZHOU
1
;
Muhammad ZUBAIR
1
;
Khalid KHAN
1
;
Shun BAI
1
;
Qing-Hua SHI
1
Author Information
- Publication Type:Journal Article
- Keywords: DNAH8; gene mutation; male infertility; multiple morphological abnormalities of the sperm flagella
- MeSH: Humans; Male; Consanguinity; Pakistan; Infertility, Male/metabolism*; Semen/metabolism*; Sperm Tail/metabolism*; Spermatozoa/metabolism*; Flagella/pathology*; Mutation
- From: Asian Journal of Andrology 2023;25(3):350-355
- CountryChina
- Language:English
- Abstract: Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate. Whole-exome sequencing (WES) is used to detect pathogenic variants in patients with MMAF. In this study, a novel homozygous frameshift variant (c.6158_6159insT) in dynein axonemal heavy chain 8 (DNAH8) from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation. Hematoxylin-eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients. Furthermore, an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa. Collectively, our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.