Mitochondrial tRNA(Thr)T15943C mutation may be a new position that affects the phenotypic expression of deafness associated 12s rRNA A1555G mutation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify secondary mutations associated with deafness in a Chinese family affected with deafness.</p><p><b>METHODS</b>The family has been subjected to clinical and molecular analyses, in addition with measurement of reactive oxygen species and doubling time after establishment of immortalized lymphocyte cell lines.</p><p><b>RESULTS</b>The results showed that the hearing loss level and audiometric configuration were discrepant among the family members with maternally transmitted hearing loss. The penetrance of hearing loss in this family was respectively 66.7% and 44.4% when aminoglycoside-induced hearing loss was included or excluded. Analysis of whole mitochondrial genome has found 33 variants as previously reported polymorphisms, except for a 12s rRNA A1555G mutation and a tRNA(Thr)T15943C mutation. Haplotype evolutionary tree has verified that this family belonged to East-Asian haplogroup F. 15943 position was located on the T-stem of the tRNA(Thr), which has destroyed the extremely conserved T-A base pair when T changed to C at this position. However, functional experiments indicated that the population doubling time in special galactose and glucose were longer, whilst the level of reactive oxygen species has increased. Compared with the control cell line groups and a family only carrying the 12s rRNA A1555G mutation, all of the three groups belonged to the same haplogroup.</p><p><b>CONCLUSION</b>Mitochondrial tRNA(Thr)T15943C mutation may act as a potential modifying factor and interact with 12s rRNA A1555G mutation, and thereby enhance the penetrance and expression of deafness.</p>

The mitochondrial tRNA(Thr) A15951G mutation may be associated with Leber's hereditary optic neuropathy in two Chinese families / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore clinical, genetic and molecular features of two Chinese Han families with Leber's hereditary optic neuropathy (LHON).</p><p><b>METHODS</b>Ophthalmologic examinations revealed variable severity and age-at-onset of visual loss among probands and other matrilineal relatives of both families. The families exhibited extremely low penetrance of visual impairment. The entire mitochondrial genome of two probands was amplified by PCR in 24 overlapping fragments using sets of oligonucleotide primers.</p><p><b>RESULTS</b>Sequence analysis of complete mitochondrial genome in the pedigrees excluded three common LHON associated mutations G11778A, G3460A and T14484C, but revealed the presence of a known homoplasmic tRNA(Thr) A15951G mutation. It also showed distinct sets of mtDNA polymorphisms belonging to Eastern Asian haplogroup D4b1. The A15951G mutation is located at the extremely conserved nucleotide (conventional position 71) of tRNA(Thr). Thus, this mutation may alter the structure and stability of mitochondrial tRNA(Thr), thereby leading to a failure in the tRNA metabolism and mitochondrial dysfunction, causing visual impairment.</p><p><b>CONCLUSION</b>The results suggested that the A15951G mutation might be involved in the pathogenesis of Leber's hereditary optic neuropathy in the two families.</p>

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

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