Whole exome sequencing identifies a novel mutation in the transglutaminase 6 gene for spinocerebellar ataxia in a Chinese family.

Autosomal dominant spinocerebellar ataxias (SCA) constitute a heterogeneous group of inherited disorders. The transglutaminase 6 (TGM6) gene was recently suggested as a SCA causative gene in Chinese SCA families. In this study, two affected members of a three-generation Chinese family with SCA characterized by progressive cerebellar ataxia and lower limb pyramidal signs were subjected to whole exome sequencing. Through bioinformatics analysis of the sequence variants in these two individuals, we identified a novel mutation in the TGM6 gene (c.1528G>C) which showed perfect co-segregation with disease phenotype in all nine members of this family. This finding confirms that mutations in TGM6 gene represent an important cause of SCA in Chinese. This study also shows that whole exome sequencing of a small number of affected individuals, leveraged on bioinformatics analysis, can be an efficient strategy for identifying causative mutations in rare Mendelian disorders.