First report of a Japanese family with spinocerebellar ataxia type 10: The second report from Asia after a report from China

Abstract

Spinocerebellar ataxia type 10 (SCA10) is an autosomal-dominant cerebellar ataxia that is variably accompanied by epilepsy and other neurological disorders. It is caused by an expansion of the ATTCT pentanucleotide repeat in intron 9 of the ATXN10 gene. Until now, SCA10 was almost exclusively found in the American continents, while no cases had been identified in Japan. Here, we report the first case of an SCA10 family from Japan. The clinical manifestations in our cases were cerebellar ataxia accompanied by epilepsy, hyperreflexia and cognitive impairment. Although the primary pathology in SCA10 in humans is reportedly the loss of Purkinje cells, brain MRI revealed frontal lobe atrophy with white matter lesions. This pathology might be associated with cognitive dysfunction, indicating that the pathological process is not limited to the cerebellum. Examination of the SNPs surrounding the SCA10 locus in the proband showed the “C-expansion-G-G-C” haplotype, which is consistent with previously reported SCA10-positive individuals. This result was consistent with the findings that the SCA10 mutation may have occurred before the migration of Amerindians from East Asia to North America and the subsequent spread of their descendants throughout North and South America.

The Geographic Diversity of Spinocerebellar Ataxias (SCAs) in the Americas: A Systematic Review

“…Almeida and colleagues were the first to perform a detailed haplotype study in Brazilian and Mexican families showing several evidences of an ancestral common origin for SCA10 in Latin America, probably from an ancestral Amerindian population. Later, however, single families from China and Japan were identified, indicating that the original mutation may have occurred before the migration of Amerindians from East Asia to North America . Screenings for SCA10 among other populations are so far negative.…”

Spinocerebellar ataxia type 10 (SCA10): Mutation analysis and common haplotype based inference suggest its rarity in Indian population

“…The reported cases share common SNPs associated with the SCA10 expansion locus proposing that SCA10 in Latin America has a common origin coming from an Amerindian populace. Recently, two SCA10 affected families has been documented in China and Japan having ATTCT expansion sharing common haplotype within the repeat region [14,15].…”

“…Recently, two SCA10 affected families has been documented in China and Japan having ATTCT expansion sharing common haplotype within the repeat region [14,15].…”

“…Previous reports have suggested the absence ATXN10 pathogenic expansion in certain Asian populations like Japanese, Chinese, and Indian [14,15]. Contrary to this definition/belief, recently SCA10 positive families have been identified in the East Asian population of China and Japan.…”

“…These findings relatively combined with the sequential dispersion of SCA10 all over Latin American countries, provide evidence for a common founder mutation [11,12]. SCA10 cases reported in patients from the USA, Mexico, Argentina, Venezuela, Colombia, Bolivia, Brazil, Peru, China and recently in Japan shared common haplotype found in the Amerindian population [5,7,[13], [14], [15], [16], [17]].…”