Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy.

• Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as 'benign cytochrome c oxidase deficiency myopathy' is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T>C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

Base Sequence

Cytochrome-c Oxidase Deficiency

genetics

pathology

physiopathology

Diagnosis

Differential

Female

Genotype

Humans

Infant

Infant

Newborn

Male

Mitochondria

metabolism

Mitochondrial Encephalomyopathies

genetics

pathology

physiopathology

Molecular Biology

Molecular Sequence Data

Muscle

Skeletal

pathology

Nucleic Acid Conformation

Pedigree

Phenotype

Point Mutation

Prognosis

Publication and Content Type

ref (subject category)

art (subject category)