1.A novel homozygous frameshift variant in DNAH8 causes multiple morphological abnormalities of the sperm flagella in a consanguineous Pakistani family.
Sobia DIL ; Asad KHAN ; Ahsanullah UNAR ; Meng-Lei YANG ; Imtiaz ALI ; Aurang ZEB ; Huan ZHANG ; Jian-Teng ZHOU ; Muhammad ZUBAIR ; Khalid KHAN ; Shun BAI ; Qing-Hua SHI
Asian Journal of Andrology 2023;25(3):350-355
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.
Humans
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Male
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Consanguinity
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Pakistan
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Infertility, Male/metabolism*
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Semen/metabolism*
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Sperm Tail/metabolism*
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Spermatozoa/metabolism*
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Flagella/pathology*
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Mutation