• PMID: 29570232
• Gene Name: STX2
• Condition: Nonsyndromic maturation arrest with multinucleated spermatocytes, nonobstructive azoospermia, male infertility
• Association: Associated
• Mutation: [c.8_12delACCGG, p.(Asp3Alafs*8)]
• Population size: 131
• Population details: 131 clinically diagnosed with nonobstructive azoospermia
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Nonsyndromic maturation arrest with multinucleated spermatocytes, nonobstructive azoospermia, male infertility

STX2 is a causative gene for nonobstructive azoospermia

Nakamura S, Kobori Y, Ueda Y, Tanaka Y, Ishikawa H, Yoshida A, Katsumi M, Saito K, Nakamura A, Ogata T, Okada H, Nakai H, Miyado M, Fukami M.

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. CI - © 2018 Wiley Periodicals, Inc. FAU - Nakamura, Shigeru AU - Nakamura S AD - Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan. AD - Department of Pediatric Urology, Jichi Medical University, Children's Medical Center Tochigi, Tochigi, Japan. FAU - Kobori, Yoshitomo AU - Kobori Y AD - Department of Urology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan. FAU - Ueda, Yoshihiko AU - Ueda Y AD - Department of Pathology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan. FAU - Tanaka, Yoko AU - Tanaka Y AD - Department of Pediatrics, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan. FAU - Ishikawa, Hiromichi AU - Ishikawa H AD - Reproduction Center, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan. FAU - Yoshida, Atsumi AU - Yoshida A AD - Reproduction Center, Kiba Park Clinic, Tokyo, Japan. FAU - Katsumi, Momori AU - Katsumi M AD - Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan. FAU - Saito, Kazuki AU - Saito K AD - Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan. FAU - Nakamura, Akie AU - Nakamura A AD - Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan. FAU - Ogata, Tsutomu AU - Ogata T AUID- ORCID: 0000-0001-7178-9991 AD - Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan. FAU - Okada, Hiroshi AU - Okada H AD - Department of Urology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan. FAU - Nakai, Hideo AU - Nakai H AD - Department of Pediatric Urology, Jichi Medical University, Children's Medical Center Tochigi, Tochigi, Japan. FAU - Miyado, Mami AU - Miyado M AD - Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.