Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Am J Med Genet A. 2013 Mar;161A(3):527-33. doi: 10.1002/ajmg.a.35784. Epub 2013 Feb 7.
Haploinsufficiency of the elastin gene (ELN) on 7q11.23 is responsible for supravalvular aortic stenosis (SVAS) and other arteriopathies in patients with Williams-Beuren syndrome (WBS). These defects occur with variable penetrance and expressivity, but the basis of this is unknown. To determine whether DNA variations in ELN could serve as genetic modifiers, we sequenced the 33 exons and immediately surrounding sequence of the ELN gene (9,455 bp of sequence) in 49 DNAs from patients with WBS and compared cardiovascular phenotypes. Four missense, and four novel intronic variants were identified from a total of 24 mostly intronic single nucleotide variations and one indel. Two missense changes were present in one patient each, one published, p.Gly610Ser in exon 27 (MAF, 0.003) and one novel, p.Cys714Tyr, in exon 33 (MAF, 0.001), were rare in the general population. To identify a statistical association between the variants identified here and cardiovascular phenotypes a larger cohort would be needed.
7q11.23 上弹性蛋白基因（ELN）的单倍体不足是导致威廉姆斯-贝伦综合征（WBS）患者的主动脉瓣上狭窄（SVAS）和其他血管病变的原因。这些缺陷具有不同的外显率和表现度，但这一现象的基础尚不清楚。为了确定 ELN 中的 DNA 变异是否可以作为遗传修饰因子，我们对 49 份 WBS 患者的 DNA 进行了 ELN 基因的 33 个外显子和紧邻序列（9455bp 序列）的测序，并比较了心血管表型。从总共 24 个主要位于内含子的单核苷酸变异和一个插入缺失中鉴定出 4 个错义突变和 4 个新的内含子变异。在一名患者中各发现了 2 个错义改变，一个是已发表的 p.Gly610Ser（外显子 27，MAF0.003），另一个是新发现的 p.Cys714Tyr（外显子 33，MAF0.001），在一般人群中均为罕见。要确定此处鉴定的变异与心血管表型之间的统计学关联，需要更大的队列。
