SEPT12 mutations cause male infertility with defective sperm annulus

Yung Che Kuo, Ying Hung Lin, Hau Inh Chen, Ya Yun Wang, Yu Wei Chiou, Hsi Hui Lin, Hsien An Pan, Ching Ming Wu, Shih Ming Su, Chao Chin Hsu, Pao Lin Kuo

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)710-719
Number of pages10
JournalHuman Mutation
Volume33
Issue number4
DOIs
Publication statusPublished - Apr 1 2012
Externally publishedYes

Fingerprint

Septins
Male Infertility
Spermatozoa
Mutation
GTP Phosphohydrolases
Guanosine Triphosphate
Asthenozoospermia
Cytokinesis
Morphogenesis
Germ Cells
Computer Simulation

Keywords

  • Annulus
  • Filament formation
  • GTPase
  • Infertility
  • SEPT12

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Kuo, Y. C., Lin, Y. H., Chen, H. I., Wang, Y. Y., Chiou, Y. W., Lin, H. H., ... Kuo, P. L. (2012). SEPT12 mutations cause male infertility with defective sperm annulus. Human Mutation, 33(4), 710-719. https://doi.org/10.1002/humu.22028

SEPT12 mutations cause male infertility with defective sperm annulus. / Kuo, Yung Che; Lin, Ying Hung; Chen, Hau Inh; Wang, Ya Yun; Chiou, Yu Wei; Lin, Hsi Hui; Pan, Hsien An; Wu, Ching Ming; Su, Shih Ming; Hsu, Chao Chin; Kuo, Pao Lin.

In: Human Mutation, Vol. 33, No. 4, 01.04.2012, p. 710-719.

Research output: Contribution to journalArticle

Kuo, YC, Lin, YH, Chen, HI, Wang, YY, Chiou, YW, Lin, HH, Pan, HA, Wu, CM, Su, SM, Hsu, CC & Kuo, PL 2012, 'SEPT12 mutations cause male infertility with defective sperm annulus', Human Mutation, vol. 33, no. 4, pp. 710-719. https://doi.org/10.1002/humu.22028
Kuo YC, Lin YH, Chen HI, Wang YY, Chiou YW, Lin HH et al. SEPT12 mutations cause male infertility with defective sperm annulus. Human Mutation. 2012 Apr 1;33(4):710-719. https://doi.org/10.1002/humu.22028
Kuo, Yung Che ; Lin, Ying Hung ; Chen, Hau Inh ; Wang, Ya Yun ; Chiou, Yu Wei ; Lin, Hsi Hui ; Pan, Hsien An ; Wu, Ching Ming ; Su, Shih Ming ; Hsu, Chao Chin ; Kuo, Pao Lin. / SEPT12 mutations cause male infertility with defective sperm annulus. In: Human Mutation. 2012 ; Vol. 33, No. 4. pp. 710-719.
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