两条前α1(IV)链,由COL4A1编码,形成三聚体,此外,由COL4A2编码的proα2(IV)链,是许多组织中基底膜的主要成分。自2005年以来,COL4A1突变已被认为是遗传性脑后畸形的常染色体显性原因。COL4A1和COL4A2突变已被报道具有更广泛的脑血管,肾,眼科,心脏,和肌肉异常,表示为“COL4A1突变相关疾病。“遗传咨询是具有挑战性的,因为广泛的表型变异和降低的外显率。在伊拉斯谟大学医学中心,在2005年至2013年期间,对183例确诊患者的COL4A1和COL4A2进行了诊断性DNA分析.总的来说,鉴定21个COL4A1和3个COL4A2突变,多见于患有头颅或其他类型的实质性出血的儿童,具有40%的高从头突变率(10/24)。在13个具有COL4A1或COL4A2突变的新家庭中的观察结果促使我们回顾临床谱。我们观察了可识别的表型模式,并提出了诊断时的筛查方案。我们的数据强调了COL4A1和COL4A2突变在脑血管疾病中的重要性。散发性患者也是如此。预后和适当监测需要有症状和无症状突变携带者的随访数据。
Two proα1(IV) chains, encoded by COL4A1, form trimers that contain, in addition, a proα2(IV) chain encoded by COL4A2 and are the major component of the basement membrane in many tissues. Since 2005, COL4A1 mutations have been known as an autosomal dominant cause of hereditary porencephaly. COL4A1 and COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities, indicated as \"COL4A1 mutation-related disorders.\" Genetic counseling is challenging because of broad phenotypic variation and reduced penetrance. At the Erasmus University Medical Center, diagnostic DNA analysis of both COL4A1 and COL4A2 in 183 index patients was performed between 2005 and 2013. In total, 21 COL4A1 and 3 COL4A2 mutations were identified, mostly in children with porencephaly or other patterns of parenchymal hemorrhage, with a high de novo mutation rate of 40% (10/24). The observations in 13 novel families harboring either COL4A1 or COL4A2 mutations prompted us to
review the clinical spectrum. We observed recognizable phenotypic patterns and propose a screening protocol at diagnosis. Our data underscore the importance of COL4A1 and COL4A2 mutations in cerebrovascular disease, also in sporadic patients. Follow-up data on symptomatic and asymptomatic mutation carriers are needed for prognosis and appropriate surveillance.