The second mutation of SYCE1 gene associated with autosomal recessive nonobstructive azoospermia.

Abstract

It is estimated that 40-50% of infertility among human couples is due to male infertility. Azoospermia is estimated to occur in 1% of all men and to be thecause of 10-20% of male infertility. Genetic defects, including single gene effects, maybe cause of azoospermia in 20-30% of affected males. Here, we aim to identify thegenetic cause of azoospermia in a man who is also affected by hereditary spastic paraplegia. The proband was subjected to whole-exome sequencing, followed by acomprehensive in silico analysis to identify the azoospermia causative gene. A novel splice site mutation c.375-2A > G in SYCE1 that is thought to be thecause of azoospermia was identified. This variant co-segregated with azoospermia status in the family that has three additional affected males. SYCE1 gene encodes synaptonemal complex (SC) central element 1 protein which contributes to the formation of the synaptonemal complex during meiosis. Syce1 null male and female mice have been shown to be infertile. There have only been two reports onthe effects of SYCE1 mutations in humans; it was shown as thecause of primary ovarian failure (POI) in one and as thecause of nonobstructive azoospermia (NOA) in another. We suggest that the mutation 375-2A > G, which affects the acceptor splice site within intron 6 of SYCE1, is the likely cause of azoospermia and subsequent infertility in the family studied. The finding constitutes the third report of SYCE1mutations that affect infertility in humans and further supports its contribution to this condition.