Mutations in DNAH8 contribute to multiple morphological abnormalities of sperm flagella and male infertility

Abstract

Asthenoteratospermia is an important cause of male infertility. Here, we report two infertile patients with severe asthenoteratospermia accompanied by new genetic abnormality. Whole-exome sequencing and bioinformatics analysis suggested that compound heterozygous mutations in DNAH8 (MIM:603337) may be responsible for multiple morphological abnormalities of the sperm flagella (MMAF). Immunofluorescence assay showed that DNAH8 protein expression was significantly decreased in the sperm tail of the patients, and electron microscopy exhibited an abnormal flagellum ultrastructure, while clinical pregnancy could be achieved by intracytoplasmic sperm injection. Therefore, the compound heterozygous mutations in the DNAH8 gene may be responsible for MMAF.

Keywords: DNAH8; MMAF; compound heterozygous mutations; whole-exome sequencing.