Inversion of the Williams Syndrome Region Is a Common Polymorphism Found More Frequently in Parents of Children With Williams Syndrome
Inversion of the Williams Syndrome Region Is a Common Polymorphism Found More Frequently in Parents of Children With Williams Syndrome
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DOI：
10.1002/ajmg.c.30258
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发表时间：
2010-05-15
影响因子：
3.1
通讯作者：
Bray-Ward, Patricia
中科院分区：
文献类型：
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作者：
Hobart, Holly H.;Morris, Colleen A.;Bray-Ward, Patricia
威廉姆斯综合征（WS）是由染色体7q11.23上约1.55 Mb的DNA（包括26个基因）缺失引起的多系统疾病，该区域由于其基因组结构而易于重组。威廉姆斯综合征染色体区域（WSCR）的缺失偶尔发生。为了更好地确定家庭复发的机会，并调查该地区的基因组重排的患病率，对257名WS儿童及其父母进行了研究。我们通过中期FISH确定先证者的缺失大小，通过分子遗传学方法确定缺失染色体的父母来源，通过间期FISH确定父母双方WSCR的倒位状态。传递亲本组WSCR倒位发生率为24.9%。相比之下，非传播父母组的倒置率（对一般人群中倒置率的合理估计）为5.8%。有没有显着的性别差异，就父母的起源为删除的染色体或倒位多态性的发生率。WSCR倒位杂合子母亲与无倒位母亲的自然流产率无差异。我们计算出，对于WSCR倒位杂合的父母，孩子患有WS的机会约为1/1，750，而没有倒位的父母的机会为1/9，500。(C)2010 Wiley-Liss，Inc.
Williams syndrome (WS) is a multisystem disorder caused by deletion of about 1.55 Mb of DNA (including 26 genes) on chromosome 7q11.23, a region predisposed to recombination due to its genomic structure. Deletion of the Williams syndrome chromosome region (WSCR) occurs sporadically. To better define chance for familial recurrence and to investigate the prevalence of genomic rearrangements of the region, 257 children with WS and their parents were studied. We determined deletion size in probands by metaphase FISH, parent-of-origin of the deleted chromosome by molecular genetic methods, and inversion status of the WSCR in both parents by interphase FISH. The frequency of WSCR inversion in the transmitting parent group was 24.9%. In contrast, the rate of inversion in the non-transmitting parent group (a reasonable estimate of the rate in the general population) was 5.8%. There were no significant gender differences with respect to parent-of-origin for the deleted chromosome or the incidence of the inversion polymorphism. There was no difference in the rate of spontaneous abortion for mothers heterozygous for the WSCR inversion relative to mothers without the inversion. We calculate that for a parent heterozygous for a WSCR inversion, the chance to have a child with WS is about 1 in 1,750, in contrast to the 1 in 9,500 chance for a parent without an inversion. (C) 2010 Wiley-Liss, Inc.