Department of Medical Genetics and Center for Rare Diseases and Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Rd, Hangzhou, 310009, China.
Nanhu Brain-Computer Interface Institute, Hangzhou, China.
Cerebellum. 2024 Oct;23(5):2197-2204. doi: 10.1007/s12311-024-01710-0. Epub 2024 Jun 13.
The CACNA1A gene encodes the alpha-1A subunit of P/Q type voltage-gated calcium channel Ca2.1, which is associated with a broad clinical spectrum and variable symptomatology. While few patients with progressive ataxia caused by CACNA1A missense variants have been reported, here we report three unrelated Chinese patients with progressive ataxia due to de novo missense variants in the CACNA1A gene, including a novel pathogenic variant (c.4999C > G) and a previously reported pathogenic variant (c.4037G > A). Our findings and a systematic literature review show the unique phenotype of progressive ataxia caused by missense variants and enlarge the genetic and clinical spectrum of CACNA1A. This suggests that in addition to routine screening for dynamic mutations, screening for CACNA1A variants is important for clinicians facing patients with progressive ataxia.
CACNA1A 基因编码 P/Q 型电压门控钙通道 Ca2.1 的α-1A 亚基，与广泛的临床谱和可变的症状有关。虽然已经报道了少数由 CACNA1A 错义变异引起进行性共济失调的患者，但在这里，我们报告了三个无关的中国患者，由于 CACNA1A 基因中的从头错义变异导致进行性共济失调，包括一种新的致病性变异（c.4999C > G）和先前报道的致病性变异（c.4037G > A）。我们的发现和系统文献回顾显示了由错义变异引起的进行性共济失调的独特表型，并扩大了 CACNA1A 的遗传和临床谱。这表明，除了常规筛查动态突变外，对于面对进行性共济失调患者的临床医生来说，筛查 CACNA1A 变异也很重要。
