A Japanese case of SCA14 with the Gly128Asp mutation

Abstract

Spinocerebellar ataxia type 14 (SCA14) is a rare form of autosomal dominant cerebellar ataxias caused by mutations in the protein kinase Cc gene (PRKCG). We have identified a Japanese patient with SCA14 who carried the Gly128Asp mutation in PRKCG. She first noticed gait unsteadiness at around age 42, and then her gait ataxia worsened very slowly for more than 20 years. At age 62, she was still ambulatory, although cerebellar ataxia was clinically evident. She is the second patient identified with the G128D mutation. Both patients with this mutation showed pure cerebellar ataxia. With only two families with SCA14 found in Japan prior to this study, the clinical features and disease-causing mutations in PRKCG are heterogeneous in the same ethnic background.

Spectrum and prevalence of autosomal dominant spinocerebellar ataxia in Hokkaido, the northern island of Japan: a study of 113 Japanese families

“…We detected one family of SCA14 displaying axial myoclonus followed by ataxia at early onset; this family has already been described , and other Japanese patients with SCA14 displayed slowly progressive cerebellar syndromes with late onset that included gait and limb ataxia, dysarthria, and saccadic pursuit. Brain MRI of these patients revealed atrophy of the cerebellum (Hiramoto et al 2006;Morita et al 2006). More recently, a Dutch family with SCA14 patients was also described with early onset, mildly generalized myoclonus (Vlak et al 2006;Verbeek et al 2005).…”

“…SCA3, SCA6 and DRPLA were higher in Japanese populations than in Caucasian populations (Maruyama et al 2002;Sasaki et al 2003;Matsumura et al 2003), whereas SCA7, SCA8, SCA17, and SCA12 are less frequent in the Japanese population (Maruyama et al 2002;Sasaki et al 2000;Matsumura et al 2003;Onodera et al 2000). SCA14 phenotype has been also reported Yabe et al 2003;Morita et al 2006), but there are no reported cases of SCA27, SCA13, or SCA5. In addition, 16q22.1-linked ADCA has been identified only in the Japanese population (Wieczorek et al 2006).…”

Spinocerebellar ataxia type 14

“…Clinical features are not identical between the mutations at the same residues (H101Q and H101Y, S119P and S119F; G123R and G123E; C131R and C131Y) nor recurrent mutations of H101Y Nolte et al, 2007a), G128D Morita et al, 2006;Miura et al, 2009) and F643L (Stevanin et al, 2004;Klebe et al, 2005). Clinical features are not identical between the mutations at the same residues (H101Q and H101Y, S119P and S119F; G123R and G123E; C131R and C131Y) nor recurrent mutations of H101Y Nolte et al, 2007a), G128D Morita et al, 2006;Miura et al, 2009) and F643L (Stevanin et al, 2004;Klebe et al, 2005).…”

SCA14 in Norway, two families with autosomal dominant cerebellar ataxia and a novel mutation in the PRKCG gene

“…Spinocerebellar ataxia type 14 (SCA14, OMIM; Mendelian Inheritance in Man 605361) is an autosomal dominant neurodegenerative disorder characterized by a mild and slowly progressive form of cerebellar ataxia. Additional symptoms and signs such as myoclonus, spasticity, hyperreflexia, dystonia, tremor and cognitive decline are described in patients (1–10). The disorder is rare, representing 1.5% of the French autosomal dominant cerebellar ataxia (ADCA) families (3) and 4% of the Dutch ADCA families (7).…”

“…To date, 23 mutations are reported (1–9, 12–18) (Table 1), mostly missense mutations, but also an in‐frame deletion in exon 4 and a deletion of a termination‐codon‐containing region in exon 18. Eighteen of the 23 mutations are concentrated in the regulatory C1 domain of the gene, and most mutations are clustered in exon 4.…”