Novel homozygous missense variants in SUN5 and DNAH10 associated with male infertility and oligoasthenoteratozoospermia.

Abstract

Genetic variants are known causes of male infertility and oligoasthenoteratozoospermia (OAT), as shown by knockout mouse models and patients with infertility. However, most OAT cases lack a definitive genetic diagnosis. Peripheral blood and semen samples were collected from a patient with OAT. Semen analysis, Papanicolaou staining, transmission electron microscopy, whole-exome sequencing (WES), Sanger sequencing, and in silico analyses, such as conservative analysis and conformational analyses, were used to investigate the genetic causes of OAT. Semen analysis revealed a notable reduction in sperm count and motility, and defects in sperm morphology. Light and electron microscopy showed numerous defects in the head-to-tail coupling apparatus of the sperm, and a small number of structural defects in the sperm flagella. WES identified two novel homozygous missense variants SUN5: c.G703A/p.A235T and DNAH10: c.A1436G/p.Q479R. The p.A235T and p.Q479R variants were predicted to generate aberrant SUN5 and DNAH10 proteins using in silico analysis. Here, we report the identification of two novel deleterious variants of SUN5 and DNAH10 associated with OAT, expanding the mutant spectrum of male infertility.