Microduplication 22q11.2: A new chromosomal syndrome
Microduplication 22q11.2: A new chromosomal syndrome
复制标题
DOI：
10.1016/j.ejmg.2009.02.008
复制
发表时间：
2009-03-01
影响因子：
1.9
通讯作者：
Portnoi, Marie-France
中科院分区：
文献类型：
--
作者：
Portnoi, Marie-France
染色体 22q11.2 区域长期以来一直与基因组疾病有关。跨越该区域的低拷贝重复序列容易发生同源重组事件，并介导导致 22q11.2 重排的非等位基因同源重组。据报道，DGS/VCFS 患者中缺失的区域出现染色体重复，从而建立了一种与 22q11.2 缺失综合征互补的新基因组重复综合征。最近的数据表明，22q11.2 微重复的频率大约是缺失频率的一半。到目前为止，已经报道了约 22q11.2 重复的无关病例。据报道，家族重复发生率很高。患者的表型差异极大，从多种缺陷到轻度学习困难，与 DGS/VCFS 具有相同的特征，包括心脏缺陷、泌尿生殖系统异常、伴有或不伴有腭裂的腭咽闭合不全，并且有些个体基本正常。表型变异的基础仍有待阐明。大多数受影响的个体都有相同的 3 Mb 重复。通过间期荧光原位杂交和其他几种分子实验室技术可以高精度诊断 22q11.2 微重复综合征。 3 Mb 重复包含一个包含 40 个基因的区域，其中包括 TBX1 基因，该基因已被证明是导致 DGS/VCFS 的主要疾病基因。有趣的是，已经观察到 TBX1 功能获得突变导致与功能丧失突变或缺失引起的单倍体不足相同的表型谱，证实 TBX1 过度表达可能是 dup22q11.2 疾病的原因。 (C) 2009 Elsevier Masson SAS。版权所有。
The chromosome 22q11.2 region has long been implicated in genomic diseases. The low-copy repeats spanning the region predispose to homologous recombination events, and mediate nonallelic homologous recombinations that result in rearrangements of 22q11.2. Chromosome duplication of the region that is deleted in patients with DGS/VCFS has been reported, establishing a new genomic duplication syndrome complementary to the 22q11.2 deletion syndrome. Recent data suggest that the frequency of the microduplications 22q11.2 is approximately half that of the deletions. Up till now about SO unrelated cases of 22q11.2 duplications have been reported. A high frequency of familial duplications has been reported. The phenotype of patients is extremely variable, ranging from multiple defects to mild learning difficulties, sharing features with DGS/VCFS, including heart defects, urogenital abnormalities, velopharyngeal insufficiency with or without cleft palate, and with some individuals being essentially normal. The basis of phenotype variability remains to be elucidated. The large majority of affected individuals have identical 3 Mb duplications. The 22q11.2 microduplication syndrome can be diagnosed with high accuracy by interphase fluorescence in situ hybridization, and several other molecular laboratory techniques. The 3 Mb duplication encompasses a region containing 40 genes including the TBX1 gene that has been shown to be the major disease gene responsible for the DGS/VCFS. Interestingly, TBX1 gain-of-function mutations, resulting in the same phenotypic spectrum as haploinsufficiency caused by loss-of-function mutations or deletions, have been observed, confirming that TBX1 overexpression might be responsible for the dup22q11.2 disorder. (C) 2009 Elsevier Masson SAS. All rights reserved.