Phenotypic Spectrum of COL4A1 Mutations: Porencephaly to Schizencephaly
Phenotypic Spectrum of COL4A1 Mutations: Porencephaly to Schizencephaly
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DOI：
10.1002/ana.23736
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发表时间：
2013-01-01
影响因子：
11.2
通讯作者：
Saitsu, Hirotomo
中科院分区：
文献类型：
--
作者：
Yoneda, Yuriko;Haginoya, Kazuhiro;Saitsu, Hirotomo
目的：最近，COL4A1基因突变在孔脑和其他脑血管疾病中被报道，通常与眼、肾和肌肉的特征相关。在本研究中，我们旨在阐明COL4A1突变的表型谱和发生率。‘方法：我们对61例孔脑畸形患者和10例脑裂畸形患者进行了COL4A1突变的筛查，发现COL4A1突变可能与脑血管供应障碍导致脑变性相似，但可以根据损伤时间进行区分。结果：15例患者中发现了COL4A1突变(21%，孔脑10例，脑裂畸形5例)，这些患者表现出各种相关的表现，包括颅内钙化、局灶性皮质发育不良、桥小脑萎缩、眼部异常、肌病、血清肌酸激酶水平升高和溶血性贫血。突变包括10个错义突变、1个无义突变、1个移码突变和3个剪接点突变。5个突变被确认为从头事件。1个突变与家族性多孔性脑畸形共分离，2个突变遗传自无症状父母。通过逆转录聚合酶链式反应在2例剪接点突变的患者中发现异常剪接。解释：我们的研究首次证实COL4A1突变与脑裂畸形和溶血性贫血有关。基于COL4A1突变在孔脑和脑裂畸形患者中的常见发现，应该考虑对患有这些疾病的儿童进行COL4A1基因检测。Ann Neurol 2013；73：48-57
Objective: Recently, COL4A1 mutations have been reported in porencephaly and other cerebral vascular diseases, often associated with ocular, renal, and muscular features. In this study, we aimed to clarify the phenotypic spectrum and incidence of COL4A1 mutations. ' Methods: We screened for COL4A1 mutations in 61 patients with porencephaly and 10 patients with schizencephaly, which may be similarly caused by disturbed vascular supply leading to cerebral degeneration, but can be distinguished depending on time of insult.Results: COL4A1 mutations were identified in 15 patients (21%, 10 mutations in porencephaly and 5 mutations in schizencephaly), who showed a variety of associated findings, including intracranial calcification, focal cortical dysplasia, pontocerebellar atrophy, ocular abnormalities, myopathy, elevated serum creatine kinase levels, and hemolytic anemia. Mutations include 10 missense, a nonsense, a frameshift, and 3 splice site mutations. Five mutations were confirmed as de novo events. One mutation was cosegregated with familial porencephaly, and 2 mutations were inherited from asymptomatic parents. Aberrant splicing was demonstrated by reverse transcriptase polymerase chain reaction analyses in 2 patients with splice site mutations.Interpretation: Our study first confirmed that COL4A1 mutations are associated with schizencephaly and hemolytic anemia. Based on the finding that COL4A1 mutations were frequent in patients with porencephaly and schizencephaly, genetic testing for COL4A1 should be considered for children with these conditions. ANN NEUROL 2013;73:48-57