Clinical and genetic characterization of 16q-linked autosomal dominant spinocerebellar ataxia in South Kyushu, Japan

Abstract

16q-ADCA (OMIM no. 117210) is an autosomal dominant spinocerebellar ataxia (AD-SCA) characterized by late-onset pure cerebellar ataxia and À16C4T substitution of the puratrophin-1 gene. Recently, a series of single-nucleotide polymorphisms (haplotype block) were found to be specific to 16q-ADCA. We screened patients with ataxia and found 62 patients, including four homozygotes who carry the C-T substitution of the puratrophin-1 gene. By further analysis of the patients with the haplotype block, we observed a single-founder effect for 16q-ADCA, even in patients who are supposed to be sporadic late cortical cerebellar atrophy (LCCA). We also observed slippage mutations of microsatellite markers, GATA01 and 17msm, in the pedigrees. We compared the clinical course of 16q-ADCA in heterozygotes and homozygotes with the haplotype block and observed no apparent gene dosage effect. 16q-ADCA accounts for 27% of AD-SCAs and is the most frequent AD-SCA in South Kyushu, Japan.

Spinocerebellar ataxia type 31 exists in Northeast China

“…Furthermore, in the present study, mild axonal sensorimotor neuropathy was identified by electromyogram. This finding is somewhat distinct from most prior reports of the disease [7][8][9]20]. Similar to our observation, Furiya et al [24] reported two cases of SCA31 accompanied by mild axonal neuropathy and orthostatic hypotension in Japan.…”

“…In the present study, we found one sporadic Chinese patient with SCA31 whose clinical characteristics were similar to those found in the patients in earlier studies of SCA31 in Japan [7][8][9]20].…”

“…Currently, in Japan, SCA31 is considered to be one of the most prevalent subtypes of ADCA with a prevalence of 10-50% in Japanese families with a history of ADCA [6][7][8][9]. However, so far almost all the cases reported with this specific substitution were in Japan; thus, whether or not SCA31 exists in other countries remains unclear.…”

“…Meanwhile, the 27 sporadic patients with ILOCA were excluded from the 9 subtypes of ADCA above mentioned. Because the −16C > T change in the puratrophin-1 gene was identified to be a marker in a strong linkage disequilibrium with SCA31 [4], we first screened this single-nucleotide change in the 12 unknown ADCA families and in the samples from the 27 sporadic patients with ILOCA by PCR-RFLP under conditions reported previously [7][8][9].…”

Prevalence of Autosomal Dominant Cerebellar Ataxia in Aomori, the Northernmost Prefecture of Honshu, Japan

“…In fact, in some areas such as South Kyushu and Nagano Prefecture, it has been found to be the most frequent ADCA subtype (27,28), making it noteworthy that SCA31 is rare (2.6% of cases) in Aomori Prefecture.…”