TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing

摘要: Autosomal-dominant spinocerebellar ataxias constitute a large, heterogeneous group of progressive neurodegenerative diseases with multiple types. To date, classical genetic studies have revealed 31 distinct forms and identified 19 causative genes. Traditional positional cloning strategies, however, limitations for finding genes rare Mendelian disorders. Here, we used combined strategy exome sequencing linkage analysis to identify novel ataxia gene, TGM6. We sequenced the whole four patients in Chinese four-generation family missense mutation, c.1550T-G transition (L517W), exon 10 This change is at highly conserved position, predicted functional impact, completely cosegregated phenotype. The results were validated using analysis. mutation was located same region (20p13-12.2) as that by analysis, which cross-validated TGM6 gene this family. also showed could be mapped method one sample from further confirmed our identifying another c.980A-G (D327G) seven an additional family, Both mutations absent 500 normal unaffected individuals matched geographical ancestry. illustrates whole-exome affected effective cost efficient mapping disorders use improving efficiency.