TY - JOUR
T1 - ATP1A3 variants and slowly progressive cerebellar ataxia without paroxysmal or episodic symptoms in children
AU - Sasaki, Masayuki
AU - Sumitomo, Noriko
AU - Shimizu-Motohashi, Yuko
AU - Takeshita, Eri
AU - Kurosawa, Kenji
AU - Kosaki, Kenjiro
AU - Iwama, Kazuhiro
AU - Mizuguchi, Takeshi
AU - Matsumoto, Naomichi
N1 - Funding Information:
This study was in part supported by the Intramural Research Grant (30‐6) for Neurological and Psychiatric Disorders of the National Center of Neurology and Psychiatry (M Sasaki), Research Committee of the Ataxia, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health and Labour Sciences Research Grants, The Ministry of Health, Labour and Welfare, Japan (M Sasaki), the Initiative on Rare and Undiagnosed Diseases (Grant number: 17ek0109151) from the Japan Agency for Medical Research and Development (K Kurosawa, K Kosaki), AMED under the grant numbers JP19ek0109280, JP19dm0107090, JP19ek0109301, JP19ek0109348, and JP18kk020501 (N Matsumoto), and JSPS KAKENHI under the grant numbers JP17H01539 (N Matsumoto). The authors declare that there is no conflict of interest to report.
Publisher Copyright:
© 2020 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press
PY - 2021/1
Y1 - 2021/1
N2 - A heterogeneous spectrum of clinical manifestations caused by mutations in ATP1A3 have been previously described. Here we report two cases of infantile-onset cerebellar ataxia, due to two different ATP1A3 variants. Both patients showed slowly progressive cerebellar ataxia without paroxysmal or episodic symptoms. Brain magnetic resonance imaging revealed mild cerebellar cortical atrophy in both patients. Whole exome sequencing revealed a de novo heterozygous variant in ATP1A3 in both patients. One patient had the c.460A>G (p.Met154Val) variant, while the other carried the c.1050C>A (p.Asp350Lys) variant. This phenotype was characterized by a slowly progressive cerebellar ataxia since the infantile period, which has not been previously described in association with ATP1A3 variants or in ATP1A3-related clinical conditions. Our report contributes to extend the phenotypic spectrum of ATP1A3 mutations, showing paediatric slowly progressive cerebellar ataxia with mild cerebellar atrophy alone as an additional clinical presentation of ATP1A3-related neurological disorders.
AB - A heterogeneous spectrum of clinical manifestations caused by mutations in ATP1A3 have been previously described. Here we report two cases of infantile-onset cerebellar ataxia, due to two different ATP1A3 variants. Both patients showed slowly progressive cerebellar ataxia without paroxysmal or episodic symptoms. Brain magnetic resonance imaging revealed mild cerebellar cortical atrophy in both patients. Whole exome sequencing revealed a de novo heterozygous variant in ATP1A3 in both patients. One patient had the c.460A>G (p.Met154Val) variant, while the other carried the c.1050C>A (p.Asp350Lys) variant. This phenotype was characterized by a slowly progressive cerebellar ataxia since the infantile period, which has not been previously described in association with ATP1A3 variants or in ATP1A3-related clinical conditions. Our report contributes to extend the phenotypic spectrum of ATP1A3 mutations, showing paediatric slowly progressive cerebellar ataxia with mild cerebellar atrophy alone as an additional clinical presentation of ATP1A3-related neurological disorders.
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U2 - 10.1111/dmcn.14666
DO - 10.1111/dmcn.14666
M3 - Article
C2 - 32895939
AN - SCOPUS:85090305658
SN - 0012-1622
VL - 63
SP - 111
EP - 115
JO - Developmental Medicine and Child Neurology
JF - Developmental Medicine and Child Neurology
IS - 1
ER -