PMC:4157140 / 8244-9525 JSONTXT

{"project":"2_test","denotations":[{"id":"25175347-12136116-2048448","span":{"begin":275,"end":277},"obj":"12136116"},{"id":"25175347-22499348-2048449","span":{"begin":405,"end":407},"obj":"22499348"},{"id":"25175347-22499348-2048450","span":{"begin":844,"end":846},"obj":"22499348"}],"text":"Mutations in SURF1 and mtDNA were excluded in individuals S1, S3, S4, and S6. Southern blot analysis showed no deletion or depletion of individual S1 muscle mtDNA, although the elevated CS activity in individual S2 muscle was accompanied by a 3-fold increase in mtDNA content14 compared to age-matched control muscle specimens (not shown). WES was subsequently performed on DNA from individuals S1 and S2;15 after filtering steps to exclude common SNPs (frequency \u003e 0.2%), we searched for homozygous or compound heterozygous variants shared by the two sisters, according to a predicted recessive mode of inheritance. From the list of genes prioritized by this procedure, we then selected (1) variants known to be associated with MRC defects and (2) novel recessive variants affecting genes that encode known or predicted mitochondrial proteins.15 As a result, a homozygous variant was identified in APOPT1, a gene on chr14q32.33 (Table 3, Figures 3A–3C). The c.235C\u003eT (RefSeq accession number NM_032374.3) nucleotide substitution is predicted to introduce a stop codon causing the synthesis of a truncated protein (p.Arg79∗; RefSeq NP_115750.2). This mutation was confirmed by Sanger sequencing in both individuals S1 and S2, and the parents were shown to be heterozygous carriers."}