Novel De Novo KCND3 Mutation in a Japanese Patient with Intellectual Disability, Cerebellar Ataxia, Myoclonus, and Dystonia

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. MR...

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Bibliographic Details
Published in:Cerebellum (London, England) England), 2018-04, Vol.17 (2), p.237-242
Main Authors: Kurihara, Masanori, Ishiura, Hiroyuki, Sasaki, Takuya, Otsuka, Juuri, Hayashi, Toshihiro, Terao, Yasuo, Matsukawa, Takashi, Mitsui, Jun, Kaneko, Juntaro, Nishiyama, Kazutoshi, Doi, Koichiro, Yoshimura, Jun, Morishita, Shinichi, Shimizu, Jun, Tsuji, Shoji
Format: Article
Language:English
Subjects:
Ataxia
Atrophy
Biomedical and Life Sciences
Biomedicine
Cerebellar ataxia
Cerebellum
DNA sequencing
Dystonia
EEG
Genetic testing
Genotypes
Glycine
Hyperventilation
Intellectual disabilities
Magnetic resonance imaging
Missense mutation
Mutation
Myoclonus
Neurobiology
Neurology
Neurosciences
Phenotypes
Short Report
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Summary: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.
ISSN:1473-4222
1473-4230
DOI:10.1007/s12311-017-0883-4