title: Clinical and genetic characterizations of 16q-linked autosomal dominant spinocerebellar ataxia (AD-SCA) and frequency analysis of AD-SCA in the Japanese population.
abstract: Autosomal dominant spinocerebellar ataxias (AD-SCAs) form a clinically and genetically heterogeneous group of neurodegenerative disorders. Recently, a single nucleotide substitution in the 5'-untranslated region of the puratrophin-1 gene was found to be associated with one type of AD-SCA linked to chromosome 16q (16q-SCA). To obtain further insight into the contribution of the C-to-T substitution in the puratrophin-1 gene to the clinical and genetic characteristics of patients with 16q-SCA, we analyzed 686 families with 719 individuals diagnosed with progressive ataxia. We found C-to-T substitution in the puratrophin-1 gene in 57 unrelated families with 65 affected individuals. The mean age at onset in the patients with 16q-SCA was 59.1 (range, 46-77). Ataxia is the most common initial symptom. The elderly patients over 65 occasionally showed other accompanying clinical features including abnormalities in tendon reflexes, involuntary movements, and reduced vibration sense. We also examined the frequency of the AD-SCA subtype, considering the effects of age at onset. In the 686 AD-SCA families, SCA6 and Machado-Joseph disease/SCA3 are frequent subtypes, followed by dentatorubral-pallidoluysian atrophy and 16q-SCA. 16q-SCA is not a rare subtype of Japanese AD-SCA, particularly in patients with ages at onset over 60.
authors.affiliation: Department of Molecular Neuroscience, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nozaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ikeuchi
authors.forename: Akio
authors.initials: A
authors.lastname: Kawakami
authors.forename: Akio
authors.initials: A
authors.lastname: Kimura
authors.forename: Reiji
authors.initials: R
authors.lastname: Koide
authors.forename: Miyuki
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: Yuusaku
authors.initials: Y
authors.lastname: Nakmura
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Mutoh
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakao
authors.forename: Ko
authors.initials: K
authors.lastname: Sahashi
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
mesh_terms: D017668:Age of Onset; D000368:Aged; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013049:Spectrin / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000453:epidemiology / Q000235:genetics*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C503982:PLEKHG4 protein, human; D013049:Spectrin; D004247:DNA