Identification of novel missense mutations of the TGFBR3 gene in Chinese women with premature ovarian failure.
The aim of this study was to assess the association between human transforming growth factor β receptor, type III (TGFBR3) and idiopathic premature ovarian failure (POF) in a Chinese population. A total of 112 Chinese women with idiopathic POF and 110 normal controls were examined. DNA samples prepared from blood leukocytes were used as templates for polymerase-chain reaction amplification of DNA fragments from TGFBR3. The gene fragments were sequenced. Web-based programs, including PolyPhen, Sorting Intolerant from Tolerant (SIFT), Prediction of Pathological Mutations (PMUT), ScanProsite and ClustalW2, were used to predict the potential functional and structural impacts of the missense variants of TGFBR3. A total of 11 novel variants were identified. Among them, six were found only in the POF patients. Two missense variants, p.E459G and p.P825L, which are conserved in primates, were predicted to have functional and structural impacts on the TGFBR3 protein. The other four variants (c.381+12A>C, c.2431-7A>G, p.S172S and p.C220C) were considered benign. However, further functional studies are necessary to confirm these findings.
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, PR China.
Chun-rong
CR
Qin
Shi-ling
SL
Chen
Ji-long
JL
Yao
Wei-qing
WQ
Wu
Jian-sheng
JS
Xie
D002681:China; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D020125:Mutation, Missense; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D020539:Sequence Analysis, Protein
D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan