STX2 is a causative gene for nonobstructive azoospermia.

STX2 encodes a sulfoglycolipid transporter. Although Stx2 nullizygosity is known to cause spermatogenic failure in mice, STX2 mutations have not been identified in humans. Here, we performed STX2 mutation analysis for 131 Japanese men clinically diagnosed with nonobstructive azoospermia. As a result, we identified a homozygous frameshift mutation [c.8_12delACCGG, p.(Asp3Alafs*8)] in one patient. The mutation-positive patient exhibited loss-of-heterozygosity for 58.4 Mb genomic regions involving STX2, suggesting possible parental consanguinity. The patient showed azoospermia, relatively small testes, and a mildly elevated follicle stimulating hormone level, but no additional clinical features. Testicular histology of the patient showed universal maturation arrest and multinucleated spermatocytes, which have also been observed in mice lacking Stx2. PCR-based cDNA screening revealed wildtype STX2 expression in various tissues including the testis. Our results indicate that STX2 nullizygosity results in nonsyndromic maturation arrest with multinucleated spermatocytes, and accounts for a small fraction of cases with nonobstructive azoospermia.