Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility.

Muhammad SHOAIB; Muhammad ZUBAIR; Wasim SHAH; Meftah UDDIN; Ansar HUSSAIN; Ghulam MUSTAFA; Fazal RAHIM; Huan ZHANG; Imtiaz ALI; Tanveer ABBAS; Yousaf RAZA; Sui-Xing FAN; Qing-Hua SHI

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Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility.

Author: Muhammad SHOAIB ¹ ; Muhammad ZUBAIR ; Wasim SHAH ; Meftah UDDIN ; Ansar HUSSAIN ; Ghulam MUSTAFA ; Fazal RAHIM ; Huan ZHANG ; Imtiaz ALI ; Tanveer ABBAS ; Yousaf RAZA ; Sui-Xing FAN ; Qing-Hua SHI
Author Information

1. Center 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.
Publication Type:Journal Article
Keywords: asthenoteratozoospermia; male infertility; multiple morphological abnormalities of sperm flagella
MeSH: Adult; Humans; Male; Alleles; Asthenozoospermia/pathology*; Axonemal Dyneins/genetics*; Dyneins/genetics*; Exome Sequencing; Infertility, Male/pathology*; Mutation; Pakistan; Pedigree; Sperm Tail/pathology*
From: Asian Journal of Andrology 2025;27(4):516-523
CountryChina
Language:English
Abstract: Multiple morphological abnormalities of sperm flagella (MMAF) is a severe form of asthenoteratozoospermia, characterized by morphological abnormalities and reduced motility of sperm, causing male infertility. Although approximately 60% of MMAF cases can be explained genetically, the etiology of the remaining cases is unclear. Here, we identified two novel compound heterozygous variants in the gene, dynein axonemal heavy chain 10 ( DNAH10 ), in three patients from two unrelated Pakistani families using whole-exome sequencing (WES), including one compound heterozygous mutation ( DNAH10 : c.9409C>A [p.P3137T]; c.12946G>C [p.D4316H]) in family 1 and another compound heterozygous mutation ( DNAH10 : c.8849G>A [p.G2950D]; c.11509C>T [p.R3687W]) in family 2. All the identified variants are absent or rare in public genome databases and are predicted to have deleterious effects according to multiple bioinformatic tools. Sanger sequencing revealed that these variants follow an autosomal recessive mode of inheritance. Hematoxylin and eosin (H&E) staining revealed MMAF, including sperm head abnormalities, in the patients. In addition, immunofluorescence staining revealed loss of DNAH10 protein signals along sperm flagella. These findings broaden the spectrum of DNAH10 variants and expand understanding of the genetic basis of male infertility associated with the MMAF phenotype.