RESUMO
The identification of disease causing mutation in patients with neurodegenerative disorders originating from small, non-consanguineous families is challenging. Three siblings were found to have ventriculomegaly at early gestation; postnatally, there was no acquisition of developmental milestones, and the muscles of the children were dystrophic. Plasma and CSF lactate levels were normal, but the activities of mitochondrial complex I and IV were markedly decreased. Using linkage analysis in the family, followed by whole exome sequencing of a single patient, we identified a pathogenic mutation in the AIFM1 gene which segregated with the disease state and was absent in 86 anonymous controls. This is the second report of a mutation in the AIFM1 gene, extending the clinical spectrum to include prenatal ventriculomegaly and underscores the importance of AIF for complex I assembly. In summary, linkage analysis followed by exome sequencing of a single patient is a cost-effective approach for the identification of disease causing mutations in small non-consanguineous families.