Frequency of mitochondrial transfer RNA mutations and deletions in 225 patients presenting with respiratory chain deficiencies

Objective-To evaluate the frequency of pathogenic mtDNA transfer RNA mutati ons and deletions in biochemically demonstrable respiratory chain (RC) defi ciencies in paediatric and adult patients. Methods-We screened for deletions and sequenced mitochondrial transfer RNA genes in skeletal muscle DNA from 225 index patients with clinical symptoms suggestive of a mitochondrial disorder and with biochemically demonstrable RC deficiency in skeletal muscle. Results-We found pathogenic mitochondrial DNA mutations in 29% of the patie nts. The detection rate was significantly higher in adults (48%) than in th e paediatric group (18%). Only one pathogenic mutation was detected in the neonatal group. In addition, we describe seven novel transfer RNA sequence variations with unknown pathogenic relevance (six homoplasmic and one heter oplasmic) and 13 homoplasmic polymorphisms. One heteroplasmic transfer RNA( Leu(UUR)) A >G mutation at position 3274 is associated with a distinct neur ological syndrome. Conclusions-We provide an estimation of the frequency of mitochondrial tran sfer RNA mutations and deletions in paediatric and adult patients with resp iratory chain deficiencies.