title: Whole mitochondrial genome analysis of a family with NARP/MILS caused by m.8993T>C mutation in the MT-ATP6 gene.
abstract: Mutations in mitochondrial DNA (mtDNA) encoded nucleotide 8993 can cause NARP syndrome (neuropathy, ataxia, and retinitis pigmentosa) or MILS (maternally inherited Leigh syndrome). The rare T8993C mutation in the MT-ATP6 gene is generally considered to be clinically milder, but there is marked clinical heterogeneity ranging from asymptomatic carriers to fatal infantile Leigh syndrome. Clinical heterogeneity has mostly been attributed to mtDNA heteroplasmy, but environmental, autosomal, tissue-specific factors, nuclear modifier genes, and mtDNA variations may also modulate disease expression. Here, we report the results of whole mitochondrial genome analysis of a family with m.8993T>C mutation in the MT-ATP6 gene and associated with NARP/MILS, and discuss the familial inheritance, effects of variation in combinations and heteroplasmy levels on the clinical findings. The whole mitochondrial genome was sequenced with ~182× average depth of coverage per sample with next-generation sequencing technology. Thus, all heteroplasmic (>%10) and homoplasmic variations were determined (except for 727C insertion) and classified according to the associations with mitochondrial diseases.
authors: Medical Faculty, Deparment of Pediatrics, Division of Child Neurology, Kocaeli University, Kocaeli, Turkey. bulentkara@excite.com
authors: Bülent
authors: B
authors: Kara
authors: Muzaffer
authors: M
authors: Arıkan
authors: Hülya
authors: H
authors: Maraş
authors: Neslihan
authors: N
authors: Abacı
authors: Aris
authors: A
authors: Cakıris
authors: Duran
authors: D
authors: Ustek
mesh_terms: D002648:Child; D004272:DNA, Mitochondrial / Q000032:analysis*; D005260:Female; D015870:Gene Expression; D018740:Genetic Heterogeneity; D054629:Genome, Mitochondrial; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000235:genetics* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000473:pathology; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; C501005:MT-ATP6 protein, human; D025261:Mitochondrial Proton-Translocating ATPases