22q11.2 distal deletion: A recurrent genomic disorder distinct from DiGeorge syndrome and velocardiofacial syndrome
22q11.2 distal deletion: A recurrent genomic disorder distinct from DiGeorge syndrome and velocardiofacial syndrome
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DOI：
10.1016/j.ajhg.2007.09.014
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发表时间：
2008-01-01
影响因子：
9.8
通讯作者：
Patel, Ankita
中科院分区：
文献类型：
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作者：
Ben-Shachar, Shay;Ou, Zhishuo;Patel, Ankita
染色体22q11.2内的微缺失导致可变表型，包括DiGeorge综合征（DGS）和腭心面综合征（VCFS）。大约97%的DGS/VCFS患者有一个常见的复发性类似3 Mb缺失或一个较小的，不太常见的，类似1.5 Mb巢式缺失。这两种缺失显然是由于位于22q11.2的非等位基因侧翼低拷贝重复（LCR）序列之间的同源重组而发生的。有趣的是，虽然八个不同的LCR位于近端22 q，只有少数情况下的非典型缺失利用替代LCR已被描述。使用基于阵列的比较基因组杂交（CGH）分析，我们已经检测到6个不相关的情况下，22q11.2内的缺失，位于远端的类似3 Mb的共同缺失区。进一步的分析表明，重排具有聚集的断点，并且分别在近端侧接LCR 22 -4和远端侧接LCR 22 -5或LCR 22 -6处存在类似于1.4 Mb或类似于2.1 Mb的复发性缺失。亲本荧光原位杂交（FISH）分析显示，没有可用的亲本（12个中有11个可用）有缺失，表明从头发生事件。所有患者均表现出特征性的面部畸形特征。早产、产前和产后生长迟缓、发育迟缓和轻度骨骼异常的病史在患者中普遍存在。两名患者被发现有心血管畸形，一个有动脉干，另一个有二叶主动脉瓣。一个病人有腭裂。我们得出结论，染色体22q11.2的远端缺失LCR 22 -4和LCR 22 -6之间，虽然他们共享一些特征性功能与DGS/VCFS，代表了一种新的基因组疾病不同的基因组和临床上从众所周知的DGS/VCF缺失综合征。
Microdeletions within chromosome 22q11.2 cause a variable phenotype, including DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). About 97% of patients with DGS/VCFS have either a common recurrent similar to 3 Mb deletion or a smaller, less common, similar to 1.5 Mb nested deletion. Both deletions apparently occur as a result of homologous recombination between nonallelic flanking low-copy repeat (LCR) sequences located in 22q11.2. Interestingly, although eight different LCRs are located in proximal 22q, only a few cases of atypical deletions utilizing alternative LCRs have been described. Using array-based comparative genomic hybridization (CGH) analysis, we have detected six unrelated cases of deletions that are within 22q11.2 and are located distal to the similar to 3 Mb common deletion region. Further analyses revealed that the rearrangements had clustered breakpoints and either a similar to 1.4 Mb or similar to 2.1 Mb recurrent deletion flanked proximally by LCR22-4 and distally by either LCR22-5 or LCR22-6, respectively. Parental fluorescence in situ hybridization (FISH) analyses revealed that none of the available parents (11 out of 12 were available) had the deletion, indicating de novo, events. All patients presented with characteristic facial dysmorphic features. A history of prematurity, prenatal and postnatal growth delay, developmental delay, and mild skeletal abnormalities was prevalent among the patients. Two patients were found to have a cardiovascular malformation, one had truncus arteriosus, and another had a bicuspid aortic valve. A single patient had a cleft palate. We conclude that distal deletions of chromosome 22q11.2 between LCR22-4 and LCR22-6, although they share some characteristic features with DGS/VCFS, represent a novel genomic disorder distinct genomically and clinically from the well-known DGS/VCF deletion syndromes.