A novel CACNA1A variant in a child with early stroke and intractable epilepsy.
A novel CACNA1A variant in a child with early stroke and intractable epilepsy.
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DOI：
10.1002/mgg3.1383
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发表时间：
2020-10
影响因子：
2
通讯作者：
Lalani SR
中科院分区：
文献类型：
--
作者：
Gudenkauf FJ;Azamian MS;Hunter JV;Nayak A;Lalani SR
CACNA 1A变异体已在几种疾病中描述，这些疾病包括广泛的神经学表型，包括偏瘫性偏头痛、共济失调、认知延迟和癫痫。迄今为止，文献中仅报告了一次CACNA 1A变异体引起的缺血性卒中。我们描述了一名4岁女性，从6周龄开始复发性缺血性中风，顽固性癫痫，严重的全球发育迟缓。完成外显子组测序（ES）以进行评价。我们在CACNA 1A中发现了一个新的、可能致病的突变体p.Leu1692Gln。这种取代影响了从鱼类到灵长类动物物种中高度保守的亮氨酸残基。我们提出了第二例复发性缺血性中风的患者与CACNA 1A突变。我们的研究结果扩大了与Cav2.1（P/Q型）钙通道功能障碍相关的表型异质性，并建议在评估儿科卒中时考虑CACNA 1A障碍。我们描述了一名4岁女性，从6周龄开始复发性缺血性卒中，顽固性癫痫和显著的整体发育迟缓，发现其在CACNA 1A中存在一种新的可能致病的p.Leu1692Gln变异。我们的报告介绍了第二个描述的情况下，复发性缺血性中风的患者与CACNA 1A突变，并扩大了表型异质性相关的变异，在这个基因。
CACNA1A variants have been described in several disorders that encompass a wide range of neurologic phenotypes, including hemiplegic migraine, ataxia, cognitive delay, and epilepsy. To date, ischemic stroke caused by a CACNA1A variant has only been reported once in the literature. We describe a 4‐year‐old female with recurrent ischemic strokes beginning at 6 weeks of age, intractable epilepsy, and significant global developmental delay. Exome sequencing (ES) was completed for her evaluation. We found a novel de novo, likely pathogenic variant, p.Leu1692Gln in CACNA1A by ES. The substitution affects a leucine residue that is highly conserved in species from fish to primates. We present the second case of recurrent ischemic strokes in a patient with CACNA1A mutation. Our findings expand the phenotypic heterogeneity related to Cav2.1 (P/Q‐type) calcium channel dysfunction and suggest consideration of CACNA1A disorder in evaluation of pediatric strokes. We describe a four‐year‐old female with recurrent ischemic strokes beginning at six weeks of age, intractable epilepsy, and significant global developmental delay, who was found to have a novel de novo likely pathogenic p.Leu1692Gln variant in CACNA1A. Our report presents the second described case of recurrent ischemic strokes in a patient with CACNA1A mutation and expands the phenotypic heterogeneity related to variants in this gene.
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影响因子：
37.8
作者：
Eikermann-Haerter K;Lee JH;Yuzawa I;Liu CH;Zhou Z;Shin HK;Zheng Y;Qin T;Kurth T;Waeber C;Ferrari MD;van den Maagdenberg AM;Moskowitz MA;Ayata C
通讯作者：
Ayata C
影响因子：
64.5
作者：
Klassen T;Davis C;Goldman A;Burgess D;Chen T;Wheeler D;McPherson J;Bourquin T;Lewis L;Villasana D;Morgan M;Muzny D;Gibbs R;Noebels J
通讯作者：
Noebels J
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
影响因子：
4.5
作者：
Luo X;Rosenfeld JA;Yamamoto S;Harel T;Zuo Z;Hall M;Wierenga KJ;Pastore MT;Bartholomew D;Delgado MR;Rotenberg J;Lewis RA;Emrick L;Bacino CA;Eldomery MK;Coban Akdemir Z;Xia F;Yang Y;Lalani SR;Lotze T;Lupski JR;Lee B;Bellen HJ;Wangler MF;Members of the UDN
通讯作者：
Members of the UDN
影响因子：
2.3
作者：
Felling, Ryan J.;Sun, Lisa R.;Bernard, Timothy
通讯作者：
Bernard, Timothy