Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth.
Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth.
复制标题
DOI：
--
复制
发表时间：
1996-10
影响因子：
9.8
通讯作者：
L. Jurado;R. Peoples;P. Kaplan;B. Hamel;U. Francke
中科院分区：
文献类型：
--
作者：
L. Jurado;R. Peoples;P. Kaplan;B. Hamel;U. Francke
威廉姆斯综合征 (WS) 是一种具有可变表型表达的发育障碍，在大多数情况下，与包括弹性蛋白基因 (ELN) 在内的染色体带 7q11.23 部分的半合子缺失有关。我们研究了缺失的频率和大小，确定了亲本起源，并将分子结果与 65 名 WS 患者的临床发现相关联。通过对两个基因内多态性进行分型、定量 Southern 分析和/或 FISH 来确定 ELN 基因座的半合性。覆盖缺失和侧翼区域的多态性标记通过遗传和物理作图的组合进行排序。对 WS 患者和可用父母的 13 种多态性进行基因分型显示，在 65 名临床定义的 WS 患者中，61 名 (94%) 具有 ELN 基因座缺失，并且在基因座 D7S489B、D7S2476、D7S613、D7S2472 和 D7S1870 处也是半合子（或无信息）。没有 ELN 缺失的四名患者在所研究的任何多态性位点上都不是半合子。所有患者的着丝粒（D7S1816、D7S1483 和 D7S653）和端粒（D7S489A、D7S675 和 D7S669）侧翼位点都是杂合的（或无信息）。最着丝粒的缺失基因座 D7S489B 和最端粒的基因座 D7S1870 之间的遗传距离为 2 cM。断点聚集在 ELN 两侧约 1 cM 处。在 39 个提供父母起源信息的家庭中，所有缺失都是从头开始的，其中 18 个来自父系，21 个来自母系。以标准化可量化格式收集的临床数据的比较显示，母体缺失组的生长迟缓和小头畸形明显更严重。父本染色体上沉默并有助于体型生长的印记基因座可能会受到缺失的影响。
Williams syndrome (WS) is a developmental disorder with variable phenotypic expression associated, in most cases, with a hemizygous deletion of part of chromosomal band 7q11.23 that includes the elastin gene (ELN). We have investigated the frequency and size of the deletions, determined the parental origin, and correlated the molecular results with the clinical findings in 65 WS patients. Hemizygosity at the ELN locus was established by typing of two intragenic polymorphisms, quantitative Southern analysis, and/or FISH. Polymorphic markers covering the deletion and flanking regions were ordered by a combination of genetic and physical mapping. Genotyping of WS patients and available parents for 13 polymorphisms revealed that of 65 clinically defined WS patients, 61 (94%) had a deletion of the ELN locus and were also hemizygous (or noninformative) at loci D7S489B, D7S2476, D7S613, D7S2472, and D7S1870. None of the four patients without ELN deletion was hemizygous at any of the polymorphic loci studied. All patients were heterozygous (or noninformative) for centromeric (D7S1816, D7S1483, and D7S653) and telomeric (D7S489A, D7S675, and D7S669) flanking loci. The genetic distance between the most-centromeric deleted locus, D7S489B, and the most-telomeric one, D7S1870, is 2 cM. The breakpoints cluster at approximately 1 cM to either side of ELN. In 39 families informative for parental origin, all deletions were de novo, and 18 were paternally and 21 maternally derived. Comparison of clinical data, collected in a standardized quantifiable format, revealed significantly more severe growth retardation and microcephaly in the maternal deletion group. An imprinted locus, silent on the paternal chromosome and contributing to statural growth, may be affected by the deletion.