• PMID: 22275165
• Gene Name: SEPTIN12
• Condition: Male infertility, defective sperm annulus
• Association: Associated
• Mutation: SEPT12 (c.266C>T/p.T89M and c.589G>A/p.D197N)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: 2019-09-12
• Other associated phenotypes: Male infertility, defective sperm annulus

SEPT12 mutations cause male infertility with defective sperm annulus

Kuo YC, Lin YH, Chen HI, Wang YY, Chiou YW, Lin HH, Pan HA, Wu CM, Su SM, Hsu CC, Kuo PL.

Septins are members of the GTPase superfamily, which has been implicated in diverse cellular functions including cytokinesis and morphogenesis. Septin 12 (SEPT12) is a testis-specific gene critical for the terminal differentiation of male germ cells. We report the identification of two missense SEPT12 mutations, c.266C>T/p.Thr89Met and c.589G>A/p.Asp197Asn, in infertile men. Both mutations are located inside the GTPase domain and may alter the protein structure as suggested by in silico modeling. The p.Thr89Met mutation significantly reduced guanosine-5'-triphosphate (GTP) hydrolytic activity, and the p.Asp197Asn mutation (SEPT12(D197N)) interfered with GTP binding. Both mutant SEPT12 proteins restricted the filament formation of the wild-type SEPT12 in a dose-dependent manner. The patient carrying SEPT12(D197N) presented with oligoasthenozoospermia, whereas the SEPT12(T89M) patient had asthenoteratozoospermia. The characteristic sperm pathology of the SEPT12(D197N) patient included defective annulus with bent tail and loss of SEPT12 from the annulus of abnormal sperm. Our finding suggests loss-of-function mutations in SEPT12 disrupted sperm structural integrity by perturbing septin filament formation. CI - © 2012 Wiley Periodicals, Inc. FAU - Kuo, Yung-Che AU - Kuo YC AD - Graduate Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lin, Ying-Hung AU - Lin YH FAU - Chen, Hau-Inh AU - Chen HI FAU - Wang, Ya-Yun AU - Wang YY FAU - Chiou, Yu-Wei AU - Chiou YW FAU - Lin, Hsi-Hui AU - Lin HH FAU - Pan, Hsien-An AU - Pan HA FAU - Wu, Ching-Ming AU - Wu CM FAU - Su, Shih-Ming AU - Su SM FAU - Hsu, Chao-Chin AU - Hsu CC