Spinocerebellar ataxia 19/22 (SCA19/22) is a rare type of autosomal dominant SCA that was previously described in 11 families. We report the case of a 30-year-old Japanese man presenting with intellectual disability, early onset cerebellar ataxia, myoclonus, and dystonia without a family history. MRI showed cerebellar atrophy, and electroencephalograms showed paroxysmal sharp waves during hyperventilation and photic stimulation. Trio whole-exome sequencing analysis of DNA samples from the patient and his parents revealed a de novo novel missense mutation (c.1150G>A, p.G384S) in KCND3, the causative gene of SCA19/22, substituting for evolutionally conserved glycine. The mutation was predicted to be functionally deleterious by bioinformatic analysis. Although pure cerebellar ataxia is the most common clinical feature in SCA19/22 families, extracerebellar symptoms including intellectual disability and myoclonus are reported in a limited number of families, suggesting a genotype–phenotype correlation for particular mutations. Although autosomal recessive diseases are more common in patients with early onset sporadic cerebellar ataxia, the present study emphasizes that such a possibility of de novo mutation should be considered.
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The work was supported by KAKENHI (Grant-in-Aid for Scientific Research on Innovative Areas (22129001 and 22129002)) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Grants-in-Aid [H23-Jitsuyoka (Nanbyo)-Ippan-004 and H26-Jitsuyoka (Nanbyo)-Ippan-080] from the Ministry of Health, Welfare, and Labor, Japan, and a grant (16kk0205001h0001) from Japan Agency for Medical Research and Development, AMED.
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Conflict of Interest
The authors declare that they have no conflict of interest.
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