BACKGROUND: Two siblings with @entity1121 and @entity1010 were diagnosed with @entity9714 based on low enzyme activity in muscle and high @entity880 / @entity2388 ratio in fibroblasts. METHODS: Whole exome sequencing results of fibroblast gDNA from one sibling was narrowed down to 190 SNPs or In/Dels in 185 candidate genes by selecting non-synonymous coding sequence base pair changes that were not present in the SNP database. RESULTS: Two compound heterozygous mutations were identified in both siblings in @entity69770 , encoding the 24  kDa subunit of Complex I. The intronic mutation ( @entity69771 ) is disease causing and has been reported before. The other mutation is novel ( @entity69772 , @entity69773 ) and predicted to cause a pathogenic frameshift in the protein. Subsequent investigation of 10 probands with @entity9714 from different families revealed homozygosity for the intronic @entity69771 mutation in a second, consanguineous family. In this family three of five siblings were affected. Interestingly, they presented with @entity8433 but no cardiac involvement. The same genotype had been reported previously in a two families but presenting with @entity1121 , @entity2421 and @entity75 . CONCLUSION: We have identified @entity69770 mutations in two families with @entity9714 , including a novel mutation. The diagnosis of @entity8433 expands the clinical phenotypes associated with the @entity69771 mutation in this gene.

Exome sequencing identifies complex I XXXX mutations as a novel cause of @entity8433 .

@entity69771 :: ('c|DEL|IVS2+1|GTAA', 'DNAMutation') :: ['c.IVS2  +  1delGTAA'] @entity69770 :: ('4729', 'Gene') :: ['NDUFV2'] @entity75 :: ('MESH:D001927', 'Disease') :: ['encephalopathy'] @entity69772 :: ('c|INS|669_670|G', 'DNAMutation') :: ['c.669_670insG'] @entity8433 :: ('MESH:D007888', 'Disease') :: ['Leigh syndrome'] @entity1010 :: ('MESH:C566985', 'Disease') :: ['brain atrophy'] @entity2421 :: ('MESH:D009123', 'Disease') :: ['trunk hypotonia'] @entity880 :: ('MESH:D019344', 'Chemical') :: ['lactate'] @entity9714 :: ('MESH:C537475', 'Disease') :: ['Complex I deficiency', 'complex I deficiency'] @entity69773 :: ('p|FS|S|224|V|3', 'ProteinMutation') :: ['p.Ser224Valfs*3'] @entity1121 :: ('MESH:D002312', 'Disease') :: ['hypertrophic cardiomyopathy'] @entity2388 :: ('MESH:D019289', 'Chemical') :: ['pyruvate']
@entity69770 :: (4729,Gene) :: ['NDUFV2']
