Infantile cardiomyopathy caused by the T14709C mutation in the mitochondrial tRNA glutamic acid gene.

A 6-week-old child presented with hypotonia, myopathy, and a rapidly worsening dilated cardiomyopathy with severe atrial and ventricular arrhythmias and pulmonary hypertension, which proved fatal at age 3 months. Biochemical analysis showed a combined deficiency of the enzymatic activities of complexes I and IV and molecular studies identified a T14709C mutation in the mitochondrial tRNA glutamic acid gene. A review of symptomatology in patients with this mutation shows that it mainly presents in childhood or young adults with mild myopathy and diabetes mellitus.

Mitochondrial encephalomyopathy due to a novel mutation in the tRNAGlu of mitochondrial DNA.

A 14-year-old boy had exercise intolerance, weakness, ataxia, and lactic acidosis. Because his muscle biopsy showed a mosaic pattern of fibers staining intensely with the succinate dehydrogenase reaction but not at all with the cytochrome c oxidase reaction, we sequenced his mitochondrial DNA and found a novel mutation (C14680A) in the gene for tRNAGlu. The mutation was present in accessible tissues from the asymptomatic mother but not from a brother with Asperger syndrome.

Mitochondrial myopathy associated with a novel mutation in mtDNA.

A 6-year-old boy had progressive muscle weakness since age 4 and emotional problems diagnosed as Asperger syndrome. His mother and two older siblings are in good health and there is no family history of neuromuscular disorders. Muscle biopsy showed ragged-red and cytochrome coxidase (COX)-negative fibers.

New DGK gene mutations in the hepatocerebral form of mitochondrial DNA depletion syndrome.

Objective: To document novel homozygous mutations in the gene for deoxyguanosine kinase (DGK) in 3 children with mitochondrial DNA depletion.

Design: Clinical features included liver failure, hypotonia, and nystagmus in 2 siblings, and liver cirrhosis, optic dysplasia, nystagmus, and microcephaly in the third patient. We sequenced the whole coding region of the DGK gene.

Clinical and genetic features in two families with MELAS and the T3271C mutation in mitochondrial DNA.

The majority of patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) have the A3243G point mutation. The much rarer T3271C mutation has been reported predominantly in Japanese subjects. Our objective was to better define the clinical phenotype and mutation load in patients with MELAS and the T3271C mutation in mitochondrial DNA.

Varying loads of the mitochondrial DNA A3243G mutation in different tissues: implications for diagnosis.

Testing for common mutations in mitochondrial DNA (mtDNA), including the A3243G MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) mutation, is routinely done in DNA isolated from blood. Since the blood level of the A3243G mutation may be low in probands and even lower in asymptomatic or oligosymptomatic maternal relatives, we assessed the proportion of A3243G mutant genomes in other accessible tissues. We studied five tissues (leukocytes, skin fibroblasts, hair roots, urinary sediment, and cheek mucosa) in 61 individuals from 22 families harboring the A3243G mutation.

Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase gamma.

Background: The mendelian forms of progressive external ophthalmoplegia (PEO) associated with multiple mitochondrial DNA deletions are clinically heterogeneous disorders transmitted as dominant or recessive traits. Autosomal dominant PEO is caused by mutations in at least 3 genes: adenine nucleotide translocator-1 (ANT1), encoding the muscle-specific adenine nucleotide translocator; chromosome 10 open reading frame 2 (C10orf2), encoding Twinkle helicase; and polymerase gamma (POLG), encoding the alpha subunit of polymerase gamma. Mutations in POLG can also cause autosomal recessive PEO, which is often associated with multisystemic disorders.