Mitochondrial tRNA valine as a recurrent target for mutations involved in mitochondrial cardiomyopathies

Abstract

The aim of this study was to identify the genetic defect in two patients having cardiac dysfunction accompanied by neurological symptoms, and in one case MRI evidence of

Cardiac Dysfunction in Mitochondrial Disease

“…Two of them, m.1628C>T and m.1644G>A, were recently published by our group. 31 Functional analysis showed a selective reduction of the steady-state level of mitochondrial tRNAVal in the patient harboring the m.1644G>A variant. 31 MDs caused by mutations in the MT-TV gene are not very common, but 3 of the 7 point mutations described so far in this gene have been associated with HCM.…”

“…31 Functional analysis showed a selective reduction of the steady-state level of mitochondrial tRNAVal in the patient harboring the m.1644G>A variant. 31 MDs caused by mutations in the MT-TV gene are not very common, but 3 of the 7 point mutations described so far in this gene have been associated with HCM. 32- 34 In accordance with these 3 reported cases, 2 of the present patients developed cardiac conduction abnormalities and HCM within a neurologi-Cardiac Dysfunction in Mitochondrial Disease tive therapies in the future.…”

Mitochondrial tRNA Valine in Cardiomyopathies

“…The m.1659 T > C can also be considered homoplasmic, because in all tissues analysed (blood, muscle, buccal epithelia, and urinary epithelia) the heteroplasmy level was higher than 98 % [ 22 ]. The transition (m.1644G > A) was shown both in heteroplasmy (85 %) [ 30 ] and homoplasmy [ 14 ]. Interestingly, the patient with the m.1644G > A mutation in homoplasmy has a more severe clinical phenotype, including cardiac involvement which was absent in the patient with the mutation in heteroplasmy (Table 7.2 ).…”

“…This may be one of the fact that has prevented the diagnosis of mitochondrial cardiomyopathies (MCMs) [ 14 ]. Nowadays, mitochondrial defects are being increasingly recognized to play an important role in the pathogenesis of hereditary cardiomyopathies [ 8 ].…”

“…These data suggest that although the MT -TV gene is not a region prone to mutation compared with other mitochondrial tRNAs, such as MT -TL , MT -TI , and MT -TK , a relatively high percentage of mutations in this gene (45 %: 5/11) are associated with MCM. In consequence, the MT -TV gene should also be included in the molecular diagnosis of patients when there is a high suspicion of MCM [ 14 ]. Interestingly, all patients with MT -TV mutations associated with MCM presented with a hypertrophic subtype ( Table 7.2 ).…”