Identification of a novel mutation in MT-TC gene in patients with idiopathic recurrent miscarriage

Background: Recurrent miscarriage (RM) is three or more consecutive pregnancy losses prior to 20 wk from the last menstrual period. There exist a small number of accepted etiologies for RPL: Genetic Factors; Anatomic Factors; Autoimmune and Endocrine Factors. Transfer RNA (tRNA) genes are essential components of protein biosynthesis in mitochondrion. These genes are hotspots for mutations. These mutations are associated with a wide spectrum of human diseases.Objective: The aim of this study was Identification of mitochondrial tRNA Cysteine gene mutations in Iranian patients with idiopathic recurrent miscarriage.Materials and Methods: We investigated possible mutations in the MT-TC gene in 100 women with idiopathic RM and 100 healthy controls by PCR-SSCP and sequencing. RM in our patients diagnosed by specialists from infertility center of Yazd, Iran. Then sequencing results analysed by bioinformatics websites and software such as Mamit-tRNA; Mito map; RNA Fold, Gene Runner and Mega4.Results: In 4 patients we found a new mutation 5762delA that cause change in tRNA secondary structure. This mutation is novel and has not previously been reported in any other disease. Conclusion: The information provided by Mamait-tRNA and RNA fold website’s databases, showed that this mutation can lead to changes in RNA secondary structure. According to Mamait-tRNA database, this mutation is in ACC domain, a preserved region in all tRNAs. RNA fold results also show a decrease in free energy indicating more stability of the mutated tRNA. Based on these results, the 5762delA mutation may be considered as a possible susceptibility factor for RM disease. More studies of mitochondrial tRNAs altogether in a larger population needed for accurate judgment.

کلیدواژه ها:

Recurrent miscarriage (RM) ، Mitochondrion ، MT-TC gene