Identification of a c.601C>G mutation in the CCM1 gene in a kindred with multiple skin, spinal and cerebral cavernous malformations
Identification of a c.601C>G mutation in the CCM1 gene in a kindred with multiple skin, spinal and cerebral cavernous malformations
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DOI：
10.1016/j.jns.2013.07.2518
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发表时间：
2013-11-15
影响因子：
4.4
通讯作者：
Friedman, Bethany
中科院分区：
文献类型：
--
作者：
Haghighi, Alireza;Fathi, Davood;Friedman, Bethany
脑海绵状血管畸形（CCM）是一种先天性血管异常，主要发生在中枢神经系统，但也可能包括其他组织如视网膜、皮肤和肝脏的病变。这些错构瘤性发育不良通常偶发发生，由动态成簇卷曲毛细血管腔组成，无可能导致头痛、癫痫发作、轻瘫、脑萎缩和局灶性神经功能缺损的脑实质介入。家族性CCM以常染色体显性遗传方式遗传，具有不完全遗传和可变表达，归因于三个基因CCM 1、CCM 2和CCM 3的突变。在这里，我们报告一个波斯血统的亲属表现出一系列的临床症状和特点，包括癫痫发作，脑和脊髓的多发性病变，和严重的角化过度皮肤毛细血管-静脉畸形。先证者CCM 1、CCM 2和CCM 3基因的桑格DNA测序和缺失/重复检测显示CCM 1 c.601&G突变。家系成员靶向突变分析证实该突变与家系中的疾病分离。这个家族说明了在其他报道的CCM家系中观察到的表型异质性，并强调了遗传检测对家族性CCM早期诊断的重要性。据我们所知，这是第一次在波斯人群中进行CCM遗传调查。(C)2013爱思唯尔有限公司版权所有。
Cerebral cavernous malformations (CCM) are congenital vascular anomalies predominantly of the central nervous system but may include lesions in other tissues such as the retina, skin, and liver. These hamartomatous dysplasias, generally occurring sporadically, consist of dynamic clustered convoluted capillary cavities without intervening brain parenchyma that may lead to headaches, seizures, paresis, cerebral hemorrhages and focal neurological deficits. Familial forms of CCM, inherited in an autosomal dominant manner with incomplete penetrance and variable expression, are attributed to mutations in three genes, CCM1, CCM2 and CCM3. Here, we report a kindred of Persian descent exhibiting a range of clinical symptoms and features that include seizures, multiple lesions of the brain and spinal cord, and severe hyperkeratotic cutaneous capillary-venous malformations. Sanger DNA sequencing and deletion/duplication testing of the CCM1, CCM2, and CCM3 genes in the proband revealed a CCM1 c.601&G mutation. Targeted mutation analysis in family members confirmed that this mutation segregated with the disease in the family. This family illustrates the phenotypic heterogeneity that has been observed in other reported CCM-pedigrees and highlights the importance of genetic testing for early diagnosis in familial CCM. To our knowledge, this is the first genetic investigation of CCM in the Persian population. (C) 2013 Elsevier B.V. All rights reserved.