Autosomal dominant cortical cerebellar atrophy (ADCCA) linked to chromosome 16q]

Clinical features of and genetic approach identifying the gene for autosomal dominant cortical cerebellar atrophy linked to chromosome 16q (16q-ADCCA) are presented. The clinical characteristics of our 6 families with 16q-ADCCA were slowly progressive pure cerebellar syndrome with late age of onset (average +/- SD years: 55.9 +/- 10.0), which contrasts with more earlier onset, prominent sensory neuropathy and pyramidal tract signs seen in spinocerebellar ataxia type 4 (SCA4) linked to the same chromosomal region. To identify the gene responsible for 16q-ADCCA, we refined the previously mapped region and found that all of our 6 families share haplotype for markers lying in about 3-cM region in 16q31-q22, indicating that the founder effect is present in this disease. We next constructed a BAC contig spanning this 3-cM region. The maximum size of this contig was estimated 5 megabase (Mb). By searching public genome databases, we first examined for the presence for expansion of tandem repeat sequences in our patients. We found more than 50 tandem repeats including 8 CAG repeats. However, we have not detected any expansion in our patients so far. We are currently examining remaining repeat sequences for expansion and also several genes that appear potential candidates from their expression and functional profiles.