Mutations of the puratrophin-1 (PLEKHG4) gene on chromosome 16q22.1 are not a common genetic cause of cerebellar ataxia in a European population.

Autosomal dominant cerebellar ataxia (ADCA) is a genetically heterogeneous group of neurodegenerative disorders with overlapping clinical presentation. Recently, a single nucleotide substitution in the 5'-untranslated region (UTR) of the puratrophin-1 (PLEKHG4) gene on chromosome 16q22.1 has been shown to be associated with ADCA in 52 unrelated Japanese families. As this mutation has so far not been investigated in other populations, we have screened 537 European patients with a clinical diagnosis of cerebellar ataxia for this specific nucleotide substitution. The mutation was not identified in our cohort. In addition, we screened the complete 5'-UTR as well as the entire coding region of this gene in 120 patients for variations that might account for their clinical symptoms. Several new rare variations were found. For none of the variations could an obvious pathogenetic relevance be postulated at this point, albeit some findings should be followed up in additional populations and by functional assays. We conclude that mutations of the puratrophin-1 gene are not a common cause of hereditary ataxia in our Caucasian population.