point mutations of mitochondrial tRNA threonine and proline in idiopathic repeated pregnancy loss

ABSTRACT

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]. The aim of this study was analysis of tRNA[Thr] and tRNA[Pro] in women with RPL. The nucleotide variations of threonine and proline were investigated in 96 women with idiopathic repeated pregnancy loss. The related mitochondrial area was amplified using a polymerase chain reaction [PCR]. The PCR products were demonstrated by 2% agarose gel electrophoresis, and all the positive samples were purified and verified by an automated DNA sequencing method. The sequence analysis revealed 4 mutations in tRNA[Thr]. These mutations were A15907G in 2 cases [2.08%], A15924G in 3 cases [3.12%], G15928A in 10 cases [10.42%] as the most common mutations and G15930A in 3 cases [3.12%] as a novel mutation. Also, the result of tRNA[pro] sequencing showed the T15972C mutation in 1 woman [1.04%] as a novel mutation. These tRNAs mutations can alter their steady state level and affect the structure of tRNAs. It results 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 is recommended to describe their etiologic role in idiopathic RPL