The contactin 4 gene locus at 3p26 is a candidate gene of SCA16.

OBJECTIVE

To identify of the gene responsible for the onset of spinocerebellar ataxia type 16 (SCA16).

METHODS

We reanalyzed the linkage of the original Japanese pedigree using updated information, including three additional subjects. We then screened all exons located in the critical region.

RESULTS

We reassigned the locus of SCA16 to 3p26.2-pter (maximum logarithm-of-odds score = 5.177) and identified only one point mutation (4,256C-->T) in the 3' untranslated region of the contactin 4 gene (CNTN4) on chromosome 3p26.2-26.3, which cosegregated with the disease. This mutation was not detected in 520 control subjects; moreover, we revised the phenotype of SCA16 from pure to complicated SCA.

CONCLUSION

The contactin 4 gene (CNTN4) is associated with cerebellar degeneration in spinocerebellar ataxia type 16. Additional studies are necessary to prove 4,256C-->T to be a causative mutation.