Revelation of a New Mitochondrial DNA Mutation (G12147A) in a MELAS/MERFF Phenotype

Abstract

Our data propose that the G12147A change, the first mutation in the transfer RNA(His) gene associated with an overlapped MELAS/MERFF phenotype, is the cause of the encephalomyopathy in this patient interfering with the overall mitochondrial protein synthesis.

Human mitochondrial transfer RNAs: Role of pathogenic mutation in disease

“…The heteroplasmic 12147 G>A mutation was found in a patient with a MELAS phenotype that eventually evolved into a MELAS/MERRF phenotype 103. The change most likely would perturb secondary and tertiary structure 103. As previously described,60 mutations in the dihydrouridine arm might cause mitochondrial dysfunction by impairing mitochondrial protein synthesis.…”

Human mitochondrial transfer RNAs: Role of pathogenic mutation in disease

“…The heteroplasmic 12147 G>A mutation was found in a patient with a MELAS phenotype that eventually evolved into a MELAS/MERRF phenotype 103. The change most likely would perturb secondary and tertiary structure 103. As previously described,60 mutations in the dihydrouridine arm might cause mitochondrial dysfunction by impairing mitochondrial protein synthesis.…”

Cognitive dysfunction and hypogonadotrophic hypogonadism in a Brazilian patient with mitochondrial neurogastrointestinal encephalomyopathy and a novel ECGF1 mutation

“…Hypogonadotropic hypogonadism has been reported in other mitochondrial encephalomyopathies, such as autosomal dominant progressive external ophthalmoplegia [10], which, like MNGIE, is a defect of the intergenomic communication, and in mitochondrial respiratory chain complex I and II deficiencies [11,12]. Hypogonadism may also be a manifestation of the MELAS and MELAS/MERRF phenotypes [13,14]. Alternatively, the hypogonadism could be in our case unrelated to the primary disease.…”

Pathogenic Mitochondrial t RNA Point Mutations: Nine Novel Mutations Affirm Their Importance as a Cause of Mitochondrial Disease

“…), at a position involved in tertiary structure formation [Helm et al., ]. Previously identified pathogenic mutations at this position include m.5521G>A (mt‐tRNA Trp [Silvestri et al., ]) and m.12147G>A (mt‐tRNA His [Melone et al., ; Taylor et al., ]), confirming the vulnerability of this position. Interestingly, the proband in this case presented with epilepsy, similar to patients with the m.8344A>G MT‐TK mutation associated with the MERRF phenotype.…”

Human mitochondrial transfer RNAs: Role of pathogenic mutation in disease

“…The heteroplasmic 12147 G>A mutation was found in a patient with a MELAS phenotype that eventually evolved into a MELAS/MERRF phenotype 103. The change most likely would perturb secondary and tertiary structure 103. As previously described,60 mutations in the dihydrouridine arm might cause mitochondrial dysfunction by impairing mitochondrial protein synthesis.…”

Cognitive dysfunction and hypogonadotrophic hypogonadism in a Brazilian patient with mitochondrial neurogastrointestinal encephalomyopathy and a novel ECGF1 mutation

“…Hypogonadotropic hypogonadism has been reported in other mitochondrial encephalomyopathies, such as autosomal dominant progressive external ophthalmoplegia [10], which, like MNGIE, is a defect of the intergenomic communication, and in mitochondrial respiratory chain complex I and II deficiencies [11,12]. Hypogonadism may also be a manifestation of the MELAS and MELAS/MERRF phenotypes [13,14]. Alternatively, the hypogonadism could be in our case unrelated to the primary disease.…”

Pathogenic Mitochondrial t RNA Point Mutations: Nine Novel Mutations Affirm Their Importance as a Cause of Mitochondrial Disease

“…), at a position involved in tertiary structure formation [Helm et al., ]. Previously identified pathogenic mutations at this position include m.5521G>A (mt‐tRNA Trp [Silvestri et al., ]) and m.12147G>A (mt‐tRNA His [Melone et al., ; Taylor et al., ]), confirming the vulnerability of this position. Interestingly, the proband in this case presented with epilepsy, similar to patients with the m.8344A>G MT‐TK mutation associated with the MERRF phenotype.…”

Human mitochondrial transfer RNAs: Role of pathogenic mutation in disease

“…The heteroplasmic 12147 G>A mutation was found in a patient with a MELAS phenotype that eventually evolved into a MELAS/MERRF phenotype 103. The change most likely would perturb secondary and tertiary structure 103. As previously described,60 mutations in the dihydrouridine arm might cause mitochondrial dysfunction by impairing mitochondrial protein synthesis.…”

Cognitive dysfunction and hypogonadotrophic hypogonadism in a Brazilian patient with mitochondrial neurogastrointestinal encephalomyopathy and a novel ECGF1 mutation

“…Hypogonadotropic hypogonadism has been reported in other mitochondrial encephalomyopathies, such as autosomal dominant progressive external ophthalmoplegia [10], which, like MNGIE, is a defect of the intergenomic communication, and in mitochondrial respiratory chain complex I and II deficiencies [11,12]. Hypogonadism may also be a manifestation of the MELAS and MELAS/MERRF phenotypes [13,14]. Alternatively, the hypogonadism could be in our case unrelated to the primary disease.…”

Pathogenic Mitochondrial t RNA Point Mutations: Nine Novel Mutations Affirm Their Importance as a Cause of Mitochondrial Disease

“…), at a position involved in tertiary structure formation [Helm et al., ]. Previously identified pathogenic mutations at this position include m.5521G>A (mt‐tRNA Trp [Silvestri et al., ]) and m.12147G>A (mt‐tRNA His [Melone et al., ; Taylor et al., ]), confirming the vulnerability of this position. Interestingly, the proband in this case presented with epilepsy, similar to patients with the m.8344A>G MT‐TK mutation associated with the MERRF phenotype.…”