Journal of Movement Disorders

Case Report

New Nonsense Variant c.2983G>T; p.Glu995* in the CACNA1A Gene Causes Progressive Autosomal Dominant Ataxia: Yannic Saathoff, Saskia Biskup, Claudia Funke, Christian Roth; J Mov Disord. 2021;14(1):70-74. Published online October 31, 2020; DOI: https://doi.org/10.14802/jmd.20082

5,993 View
106 Download
2 Web of Science
2 Crossref

The genetic testing of hereditary ataxias includes screening for CAG-repeat expansions as well as pathogenic variants and nontranslated oligonucleotide expansion, which can cause spinocerebellar ataxia (SCA). Genotype-phenotype correlations of several SCA subtypes are difficult to establish, and the underlying mechanisms remain unclear. Here, we report a 58-year-old male patient who presented with severe generalized ataxia, horizontal gaze-evoked nystagmus, cognitive impairment and a positive family history of gait difficulties. Genetic panel diagnostics revealed a new nonsense pathogenic variant in the CACNA1A gene (c.2983G>T; p. Glu995*) that segregated with the phenotype in three clinically affected family members. This gene is related to SCA type 6 (SCA6), episodic ataxia type 2, familial hemiplegic migraine type 1, among others. When it is supported by the clinical findings and family history, additional DNA sequencing beyond fragment length analysis should be performed.

Citations

Citations to this article as recorded by

The genotype–phenotype correlations of the CACNA1A-related neurodevelopmental disorders: a small case series and literature reviews
Miriam Kessi, Baiyu Chen, Nan Pang, Lifen Yang, Jing Peng, Fang He, Fei Yin
Frontiers in Molecular Neuroscience.2023;[Epub] CrossRef
Next-Generation Sequencing Technologies and Neurogenetic Diseases
Hui Sun, Xiao-Rong Shen, Zi-Bing Fang, Zong-Zhi Jiang, Xiao-Jing Wei, Zi-Yi Wang, Xue-Fan Yu
Life.2021; 11(4): 361. CrossRef

Original Article

Genetic Screening for Spinocerebellar Ataxia Genes in a Japanese Single-Hospital Cohort: Ryuji Sakakibara, Fuyuki Tateno, Masahiko Kishi, Yohei Tsuyusaki, Yosuke Aiba, Hitoshi Terada, Tsutomu Inaoka, Setsu Sawai, Satoshi Kuwabara, Fumio Nomura; J Mov Disord. 2017;10(3):116-122. Published online August 8, 2017; DOI: https://doi.org/10.14802/jmd.17011

8,912 View
206 Download
4 Web of Science
5 Crossref

Abstract PDF

Objective
Diagnosis of sporadic cerebellar ataxia is a challenge for neurologists. A wide range of potential causes exist, including chronic alcohol use, multiple system atrophy of cerebellar type (MSA-C), and sporadic late cortical cerebellar atrophy. Recently, an autosomal-dominant spinocerebellar ataxia (SCA) mutation was identified in a cohort of patients with non-MSA-C sporadic cerebellar ataxia. The aim of this study is to genetically screen genes involved in SCA in a Japanese single-hospital cohort.
Methods
Over an 8-year period, 140 patients with cerebellar ataxia were observed. There were 109 patients with sporadic cerebellar ataxia (no family history for at least four generations, 73 patients with MSA-C, and 36 patients with non-MSA-C sporadic cerebellar ataxia) and 31 patients with familial cerebellar ataxia. We performed gene analysis comprising SCA1, 2, 3, 6, 7, 8, 12, 17, 31, and dentatorubro-pallidoluysian atrophy (DRPLA) in 28 of 31 non-MSA-C sporadic patients who requested the test. Familial patients served as a control.
Results
Gene abnormalities were found in 57% of non-MSA-C sporadic cerebellar ataxia cases. Among patients with sporadic cerebellar ataxia, abnormalities in SCA6 were the most common (36%), followed by abnormalities in SCA1 (7.1%), SCA2 (3.6%), SCA3 (3.6%), SCA8 (3.6%), and DRPLA (3.6%). In contrast, gene abnormalities were found in 75% of familial cerebellar ataxia cases, with abnormalities in SCA6 being the most common (29%). For sporadic versus familial cases for those with SCA6 abnormalities, the age of onset was older (69 years vs. 59 years, respectively), and CAG repeat length was shorter (23 vs. 25, respectively) in the former than in the latter (not statistically significant).
Conclusion
Autosomal-dominant mutations in SCA genes, particularly in SCA6, are not rare in sporadic cerebellar ataxia. The reason for the frequency of mutations in SCA6 remains unclear; however, the reason may reflect a higher age at onset and variable penetrance of SCA6 mutations.

Citations

Citations to this article as recorded by

MRI CNS Atrophy Pattern and the Etiologies of Progressive Ataxias
Mario Mascalchi
Tomography.2022; 8(1): 423. CrossRef
An atypical course of a 71-year old man with right arm weakness and ataxia: Expert commentary
Norlinah Mohamed Ibrahim
Parkinsonism & Related Disorders.2022; 105: 157. CrossRef
A novel clinicopathologic entity causing rapidly progressive cerebellar ataxia?
Shunsuke Koga, Shan Ali, Matthew C. Baker, Klaas J. Wierenga, Michelle Dompenciel, Dennis W. Dickson, Zbigniew K. Wszolek
Parkinsonism & Related Disorders.2022; 105: 149. CrossRef
The First Case of Spinocerebellar Ataxia Type 8 in Monozygotic Twins
Jun Sawada, Takayuki Katayama, Takashi Tokashiki, Shiori Kikuchi, Kohei Kano, Kae Takahashi, Tsukasa Saito, Yoshiki Adachi, Yuji Okamoto, Akiko Yoshimura, Hiroshi Takashima, Naoyuki Hasebe
Internal Medicine.2020; 59(2): 277. CrossRef
The role of gene variants in the pathogenesis of neurodegenerative disorders as revealed by next generation sequencing studies: a review
Shirley Yin-Yu Pang, Kay-Cheong Teo, Jacob Shujui Hsu, Richard Shek-Kwan Chang, Miaoxin Li, Pak-Chung Sham, Shu-Leong Ho
Translational Neurodegeneration.2017;[Epub] CrossRef

First
Prev
Page of 1
Next
Last

Search