Exome sequencing reveals SCO2 mutations in a family presented with fatal infantile hyperthermia

We applied whole-exome sequencing (WES) for identification of an underlying genetic cause of a disease in a family presented with fatal infantile hyperthermia. Analysis of WES results revealed novel, deleterious compound missense mutations, Val160Ala and Pro233Thr, in the synthesis of cytochrome C oxidase 2 gene (SCO2) encoding a mitochondrial protein, Sco2, which is important for cytochrome C oxidase (COX) synthesis. Autosomal recessive mutations in SCO2 are known to be associated with COX deficiency recognized as fatal infantile cardio-encephalomyopathy (604272, OMIM). The Val160Ala and Pro233Thr mutations occurred in the conserved thioredoxin domain of Sco2 and predicted to disrupt protein folding and interaction of Sco2 with other proteins. Our results show applicability of WES in identification of disease-causing mutations and in establishing molecular diagnosis of severe, infantile onset disorder with a challenging diagnosis.