Morris C A, Mervis C B
Department of Pediatrics, Division of Genetics, University of Nevada School of Medicine, Las Vegas, NV 89102, USA.
Annu Rev Genomics Hum Genet. 2000;1:461-84. doi: 10.1146/annurev.genom.1.1.461.
Three clinical conditions displaying phenotypic overlap have been linked to mutation or deletion of the elastin gene at 7q11.23. Supravalvar aortic stenosis, an autosomal dominant disorder characterized by elastin arteriopathy, is caused by mutation or intragenic deletions of ELN resulting in loss of function. Autosomal dominant cutis laxa, a primarily cutaneous condition, is the result of frameshift mutations at ELN that cause a dominant-negative effect on elastic fiber structure. Williams syndrome, a neurodevelopmental disorder is due to a 1.5 Mb deletion that includes ELN and at least 15 contiguous genes. The disorder is characterized by dysmorphic facies, mental retardation or learning difficulties, elastin arteriopathy, a unique cognitive profile of relative strength in auditory rote memory and language and extreme weakness in visuospatial constructive cognition, and a typical personality that includes overfriendliness, anxiety, and attention problems. The understanding of these disorders has progressed from phenotypic description to identification of causative mutations and insight into pathogenetic mechanisms for some aspects of the phenotype.
三种表现出表型重叠的临床病症与7q11.23处弹性蛋白基因的突变或缺失有关。主动脉瓣上狭窄是一种以弹性蛋白动脉病为特征的常染色体显性疾病，由ELN的突变或基因内缺失导致功能丧失引起。常染色体显性遗传性皮肤松弛症主要是一种皮肤病症，是ELN发生移码突变的结果，该突变对弹性纤维结构产生显性负效应。威廉姆斯综合征是一种神经发育障碍，是由于一个1.5 Mb的缺失，该缺失包括ELN和至少15个相邻基因。该病症的特征为面部畸形、智力迟钝或学习困难、弹性蛋白动脉病、在听觉死记硬背记忆和语言方面相对较强而在视觉空间建构认知方面极度薄弱的独特认知特征，以及包括过度友善、焦虑和注意力问题在内的典型性格。对这些病症的认识已从表型描述发展到致病突变的鉴定以及对表型某些方面致病机制的深入了解。
