22q11.2区DNA拷贝数变异与腭心面综合征临床表型关系的研究

Correlation between Copy Number Variations on 22q11.2 and Phenotypic Spectrum of Velocardiofacial Syndrome Patients

目的:分析不同临床表型腭心面综合征患者在22q11.2区的DNA拷贝数变异类型,探讨二者的关系。方法:55例临床诊断为腭心面综合征患者的DNA,经过多重连接依赖探针扩增技术检测,记录临床表型。结果 :44例(80.0%)患者在22q11.2区有DNA拷贝数变异,其中43例(78.2%)出现22q11.2杂合性缺失,1例(1.8%)为22q11.2复制。在43例22q11.2缺失患者中,40例(93.0%)为3Mb典型缺失,3例(7.0%)为1.5Mb的近端缺失。另外,这43例患者均表现为典型面容和腭咽部畸形,37例(86.0%)表现出认知和行为障碍,23例(53.5%)有自身免疫功能缺陷,10例(23.3%)表现先天性心脏病。所有表现典型面容的患者均出现了22q11.2缺失,但3Mb缺失和1.5Mb缺失患者的临床表型没有明显不同。结论:典型面容可被认为是临床直接诊断腭心面综合征22q11.2缺失的重要依据。

Objective： To analyze whether the variable expressivity of the main clinical findings of velocardiofacial syndrome （VCFS） patients are related to types of copy number variations （CNVs）on chromosome 22ql 1.2 . Methods： 55 Chinese patients clinically diagnosed as VCFS were detected by multiplex ligation-dependent probe amplification （MLPA）. The data of molecular diagnosis analyzed by MLPA and all of the clinical features presenting here were documented in detail. Results： 44 patients （80.0%） were screened out having CNVs on 22q11.2. Among these, 43 patients （78.2%） presented 22ql 1.2 heterozygous deletions, of whom 40 patients （93.0%） had typical 3Mb deletion, 3 patients （7.0%） had proximal 1.5Mb deletion. Of the 43 22ql 1.2 deletions patients 43 patients （100%） had typical face and palatal anomalies, 37 patients （86.0%） had cognitive or behavioral disorders, 23 patients （53.5%） had immune deficiency, and 10 patients （23.3%） had congenital heart diseases. Interestingly, all of the patients who presented with a typical face had 22q11.2 heterozygous deletions, but there is no different of phenotypic spectrum between the 3Mb and 1.5Mb deletion. Conclusion： Typical face should be a key factor for directly diagnosis of 22q11.2 deletions in VCFS patients.