Identification of novel missense mutations of the TGFBR3 gene in Chinese women with premature ovarian failure

The causes of premature ovarian failure are diverse and largely idiopathic. Down-regulation of the FSH concentrations by inhibins is mediated through its receptor, human transforming growth factor β receptor, type III (TGFBR3) in the gonadotrophs. The aim of this study was to assess the association between human TGFBR3 and idiopathic POF in a Chinese population. 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 two novel missense variants, p.E459G and p.P825L, on the TGFBR3 protein. These mutations were predicted to have functional impacts on the protein and are likely to be pathogenic. However, further functional studies are necessary to confirm these findings.