Respiratory chain XXXX caused by mitochondrial DNA mutations.

@entity1 @entity23706 @entity8433 @entity9714 @entity2383
Defects of the mitochondrial respiratory chain are associated with a diverse spectrum of clinical phenotypes, and may be caused by mutations in either the nuclear or the mitochondrial genome (mitochondrial DNA (mtDNA)). Isolated @entity9714 is the most common enzyme defect in @entity2383 , particularly in @entity1 in whom family history is often consistent with sporadic or autosomal recessive inheritance, implicating a nuclear genetic cause. In contrast, although a number of recurrent, pathogenic mtDNA mutations have been described, historically, these have been perceived as rare causes of paediatric @entity9714 . We reviewed the clinical and genetic findings in a large cohort of 109 paediatric @entity1 with isolated @entity9714 from 101 families. Pathogenic mtDNA mutations were found in 29 of 101 probands (29%), 21 in @entity23706 subunit genes and 8 in mtDNA tRNA genes. Nuclear gene defects were inferred in 38 of 101 (38%) probands based on cell hybrid studies, mtDNA sequencing or mutation analysis (nuclear gene mutations were identified in 22 probands). @entity8433 was the most common clinical presentation in both mtDNA and nuclear genetic defects. The median age at onset was higher in mtDNA @entity1 (12 months) than in @entity1 with a nuclear gene defect (3 months). However, considerable overlap existed, with onset varying from 0 to >60 months in both groups. Our findings confirm that pathogenic mtDNA mutations are a significant cause of @entity9714 in @entity1 . In the absence of parental consanguinity, we recommend whole mitochondrial genome sequencing as a key approach to elucidate the underlying molecular genetic abnormality.
