Tassabehji May, Urban Zsolt
Academic Unit of Medical Genetics, The University of Manchester, St Mary's Hospital, Manchester, United Kingdom.
Methods Mol Med. 2006;126:129-56. doi: 10.1385/1-59745-088-X:129.
Supravalvular aortic stenosis (SVAS) is a congenital heart disease that can occur as an isolated autosomal-dominant condition or as part of the developmental disorder Williams-Beuren syndrome (WBS) and is caused by heterozygous genetic lesions involving the elastin (ELN) gene locus on chromosome 7ql 1.23. SVAS is one of many phenotypic features associated with the contiguous gene microdeletion disorder, WBS, and is caused by deletion of the ELN locus on one chromosome 7 homolog. Point mutations, chromosomal deletions, and translocation involving ELN have also been described in individuals with nonsyndromic SVAS. In addition, ELN is involved in the connective tissue disorder, autosomal-dominant cutis laxa, and has been implicated as a susceptibility gene for hypertension and intracranial aneurysms. The molecular analysis of ELN defects is, therefore, an area of significant interest. Genetic screening can be achieved using a variety of techniques to detect both mutations and gross chromosome rearrangements involving the ELN locus, providing the ability to screen families and individuals with SVAS and associated elastinopathies.
瓣上主动脉狭窄（SVAS）是一种先天性心脏病，可作为一种孤立的常染色体显性疾病出现，也可作为威廉姆斯-贝伦综合征（WBS）发育障碍的一部分，由涉及7号染色体q11.23上弹性蛋白（ELN）基因座的杂合子遗传病变引起。SVAS是与连续性基因微缺失疾病WBS相关的众多表型特征之一，由一条7号染色体同源物上的ELN基因座缺失引起。在非综合征性SVAS患者中也描述了涉及ELN的点突变、染色体缺失和易位。此外，ELN还与结缔组织疾病常染色体显性皮肤松弛症有关，并被认为是高血压和颅内动脉瘤的易感基因。因此，ELN缺陷的分子分析是一个备受关注的领域。可以使用多种技术进行基因筛查，以检测涉及ELN基因座的突变和染色体大片段重排，从而能够对患有SVAS和相关弹性蛋白病的家庭和个体进行筛查。
