Objectives: To map the disease locus and to identify a gene mutation in a Japanese family with autosomal dominant cerebellar ataxia.
Design: A genome-wide linkage analysis was performed using the Affymetrix genome-wide human single-nucleotide polymorphism array containing 909 622 single-nucleotide polymorphisms. Direct nucleotide sequencing of a candidate gene was performed.
Setting: Hokkaido University Graduate School of Medicine and Tokyo University Graduate School of Medicine. Patients Four affected and 6 healthy individuals in a family with autosomal dominant cerebellar ataxia.
Results: One locus on chromosome 5q had a multipoint logarithm of odds score of 2.408, the theoretical maximum. This locus was flanked by markers rs681591 and rs32582 and includes PPP2R2B (protein phosphatase 2, regulatory subunit B, beta isoform), the causative gene of autosomal dominant spinocerebellar ataxia 12 (SCA12). However, unlike SCA12, no CAG repeat expansions in the promoter region and no nucleotide substitution or insertion-deletion mutations in the exons of the PPP2R2B gene were found.
Conclusion: Autosomal dominant cerebellar ataxia mapping to 5q31-q33.1 has no CAG repeat expansion or other mutations of the PPP2R2B gene.