Two dominantly inherited ataxias linked to chromosome 16q22.1: SCA4 and SCA31 are not allelic.

Autosomal dominant spinocerebellar ataxias (SCAs) are heterogeneous neurological disorders characterised by cerebellar dysfunction mostly due to Purkinje cell degeneration. Genetically, 30 different loci have been identified so far whereas the corresponding gene has not yet been determined for 12 of them. The chromosomal location for the spinocerebellar ataxia type 31 (SCA31) has been mapped to chromosome 16q22.1. This region is located within the candidate interval for the spinocerebellar ataxia type 4 (SCA4), for which the underlying mutation still has to be discovered. Recently, a complex (TGGAA)(n) containing repeat insertion within the SCA31 critical region was reported to be causative for SCA31. Although the presence of the pentanucleotide repeat component (TGGAA)(n) seems to be a specific feature of SCA31 patients' insertions, it is still unclear whether a large insertion lacking any (TGGAA) sequence remains nonpathogenic. In order to check whether the German SCA4 patients, belonging to one of the two currently known SCA4 families worldwide, exhibit a potential pathogenic mutation at the SCA31 locus, we performed molecular genetic analyses for affected as well as unaffected family members. Based on a nested-PCR approach and direct sequencing, a disease causing mutation at the SCA31 locus could be excluded for the German SCA4 kindred. However, our data impressively demonstrate the genetic instability in this chromosomal region.