PMID- 22275165
OWN - NLM
STAT- MEDLINE
DCOM- 20120709
LR  - 20191030
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Linking)
VI  - 33
IP  - 4
DP  - 2012 Apr
TI  - SEPT12 mutations cause male infertility with defective sperm annulus.
PG  - 710-9
LID - 10.1002/humu.22028 [doi]
AB  - 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  - (c) 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
FAU - Kuo, Pao-Lin
AU  - Kuo PL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120220
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 3.6.1.- (SEPTIN12 protein, human)
RN  - EC 3.6.1.- (Septins)
SB  - IM
MH  - Asthenozoospermia/genetics
MH  - Case-Control Studies
MH  - Guanosine Triphosphate/metabolism
MH  - Humans
MH  - Infertility, Male/*genetics
MH  - Male
MH  - *Mutation, Missense
MH  - Septins/chemistry/*genetics/metabolism
MH  - Sperm Motility/genetics
MH  - Spermatogenesis/genetics
MH  - Spermatozoa/abnormalities
EDAT- 2012/01/26 06:00
MHDA- 2012/07/10 06:00
CRDT- 2012/01/26 06:00
PHST- 2011/04/15 00:00 [received]
PHST- 2012/01/03 00:00 [accepted]
PHST- 2012/01/26 06:00 [entrez]
PHST- 2012/01/26 06:00 [pubmed]
PHST- 2012/07/10 06:00 [medline]
AID - 10.1002/humu.22028 [doi]
PST - ppublish
SO  - Hum Mutat. 2012 Apr;33(4):710-9. doi: 10.1002/humu.22028. Epub 2012 Feb 20.