Identification of mitochondrial tRNA leucine (CUN) gene mutation in Iranian patients with idiopathic recurrent miscarriage

Background: Mitochondrial transfer RNAs (tRNA) genes are essential components of protein biosynthesis. These genes are hotspots for mutations. These mutations are associated with a wide spectrum of human disease. Many genetic factors are known in assessment of repeated pregnancy loss (RPL).Objective: The aim of this study was identification of mitochondrial tRNA leucine (CUN) gene mutations in Iranian patients with idiopathic recurrent miscarriage.Materials and Methods: The nucleotide variations of Leucine (CUN) and Histidine were investigated in 100 women with idiopathic repeated pregnancy loss. The related mitochondrial area was amplified using polymerase chain reaction (PCR). The PCR products were demonstrated by 2% agarose gel electrophoresis, all PCR products were run on SSCP gels and the samples showed considerable band shifts due to possible mutations were sent for DNA sequencing. Nucleotide variations were found in sequencing data, studied for further information under bioinformatics websites and software.Results: The sequence analysis revealed 2 mutations in tRNAleu and 3 mutations in tRNAhis. These mutations were 12308A> G in 2 cases and 12192A> G in 1 case, as the most common mutations. Also, the results of tRNAhis sequencing showed the 12172G> A in 2 cases in 2 women as a novel mutation.Conclusion: These tRNAs mutations can alter their steady state level and affect the structure of tRNAs. They may result in protein synthesis defects and, in turn, mitochondrial dysfunction. The mutations of these genes may help in the assessment of RPL. Further study of an expanded series of these tRNA mutants in a larger size population, is recommended to describe their etiologic role in idiopathic RPL.

Keywords:

Repeated pregnancy loss , Mitochondrion , Mutation , tRNAleu (CUN) , PCR-SSCP