Yang Chen, Huang Cheng-Hung, Cheong Mei-Leng, Hung Kun-Long, Lin Lung-Huang, Yu Yeong-Seng, Chien Chih-Cheng, Huang Huei-Chen, Chen Chan-Wei, Huang Chi-Jung
Division of Genetics, Department of Pediatrics, Taipei Medical University Hospital, Taipei 11031, Taiwan.
BMC Med Genet. 2009 Feb 25;10:16. doi: 10.1186/1471-2350-10-16.
Chromosome 22q11 deletion syndrome (22q11DS) causes a developmental disorder during the embryonic stage, usually because of hemizygous deletions. The clinical pictures of patients with 22q11DS vary because of polymorphisms: on average, approximately 93% of affected individuals have a de novo deletion of 22q11, and the rest have inherited the same deletion from a parent. Methods using multiple genetic markers are thus important for the accurate detection of these microdeletions.
We studied 12 babies suspected to carry 22q11DS and 18 age-matched healthy controls from unrelated Taiwanese families. We determined genomic variance using microarray-based comparative genomic hybridization (array-CGH), quantitative real-time polymerase chain reaction (qPCR) and multiplex ligation-dependent probe amplification (MLPA).
Changes in genomic copy number were significantly associated with clinical manifestations for the classical criteria of 22q11DS using MPLA and qPCR (p < 0.01). An identical deletion was shown in three affected infants by MLPA. These reduced DNA dosages were also obtained partially using array-CGH and confirmed by qPCR but with some differences in deletion size.
Both MLPA and qPCR could produce a clearly defined range of deleted genomic DNA, whereas there must be a deleted genome that is not distinguishable using MLPA. These data demonstrate that such multiple genetic approaches are necessary for the unambiguous molecular detection of these types of complicated genomic syndromes.
22号染色体长臂11区缺失综合征（22q11DS）通常由于半合子缺失导致胚胎期发育障碍。22q11DS患者的临床表现因基因多态性而有所不同：平均而言，约93%的受累个体有22q11的新发缺失，其余则从父母一方遗传了相同的缺失。因此，使用多种遗传标记的方法对于准确检测这些微缺失很重要。
我们研究了12名疑似携带22q11DS的婴儿以及18名来自台湾无关家庭的年龄匹配的健康对照。我们使用基于微阵列的比较基因组杂交（array-CGH）、定量实时聚合酶链反应（qPCR）和多重连接依赖探针扩增（MLPA）来确定基因组变异。
使用MLPA和qPCR，基因组拷贝数的变化与22q11DS经典标准的临床表现显著相关（p < 0.01）。MLPA显示三名患病婴儿存在相同的缺失。使用array-CGH也部分获得了这些减少的DNA剂量，并通过qPCR得到证实，但缺失大小存在一些差异。
MLPA和qPCR都能产生明确界定的缺失基因组DNA范围，而必然存在使用MLPA无法区分的缺失基因组。这些数据表明，对于这些类型复杂基因组综合征的明确分子检测，此类多种遗传方法是必要的。
