AP-HP, Groupe hospitalier Lariboisière-Fernand Widal, Laboratoire de Génétique, GHU Nord, Paris, France.
Neurogenetics. 2010 Feb;11(1):101-6. doi: 10.1007/s10048-009-0208-y. Epub 2009 Jul 25.
Episodic ataxia is an autosomal dominant ion channel disorder characterized by paroxysmal attacks of incoordination. Episodic ataxia type 2 (EA2) is caused by mutations in CACNA1A. EA2 mutations are mostly nonsense and sometimes missense mutations. However, in some typical EA2 families, CACNA1A sequencing does not detect any point mutation. Herein, we have designed a quantitative multiplex polymerase chain reaction of short fluorescent fragment test to screen the 50 exons of CACNA1A and investigated 27 probands referred for molecular diagnosis of EA2 who did not show any point mutation in CACNA1A. We have identified four different exonic deletions in four patients with a typical EA2 phenotype. These results establish the need to complete sequencing analysis by a screening for deletions to ensure an accurate molecular diagnosis of EA2.
发作性共济失调是一种常染色体显性离子通道病，其特征是发作性共济失调。发作性共济失调 2 型（EA2）是由 CACNA1A 突变引起的。EA2 突变大多为无义突变，有时也为错义突变。然而，在一些典型的 EA2 家族中，CACNA1A 测序未检测到任何点突变。在此，我们设计了一种定量多重聚合酶链反应短荧光片段检测法，以筛选 CACNA1A 的 50 个外显子，并对 27 名被转介进行 EA2 分子诊断但 CACNA1A 未显示任何点突变的先证者进行了研究。我们在 4 名具有典型 EA2 表型的患者中发现了 4 种不同的外显子缺失。这些结果表明，需要通过缺失筛选来完成测序分析，以确保 EA2 的准确分子诊断。
