Two high throughput technologies to detect segmental aneuploidies identify new Williams-Beuren syndrome patients with atypical deletions
Two high throughput technologies to detect segmental aneuploidies identify new Williams-Beuren syndrome patients with atypical deletions
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DOI：
10.1136/jmg.2005.034009
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发表时间：
2006-03-01
影响因子：
4
通讯作者：
Reymond, A
中科院分区：
文献类型：
--
作者：
Howald, C;Merla, G;Reymond, A
目的：发展和比较两种诊断连续基因综合征Williams-Beuren综合征（WBS）的新技术。方法：第一种提出的方法，称为旁系序列定量（PSQ），是基于使用位于不同染色体上的旁系序列，并使用焦磷酸测序技术定量这些位点上存在的特定错配。第二种利用定量实时聚合酶链反应（QPCR）来评估分析位点的相对数量。结果：任何一种技术（分别为n=165和n=155）对100%的分析样本都获得了正确和明确的诊断。这些方法允许在182例WBS患者队列中确定2例非典型缺失患者。两例患者均表现为轻度面部异常，轻度智力迟钝伴视觉空间认知障碍，瓣上主动脉狭窄，生长指标正常。这些观察结果与GTF2IRD1或GTF2I参与一些WBS面部特征是一致的。结论：PSQ和QPCR都是稳健的，易于解释，易于建立。它们代表了在临床实验室诊断节段性非整倍体的竞争性选择。与荧光原位杂交或微卫星/SNP基因分型检测短片段非整倍体相比，它们具有优势，因为前者成本高且劳动密集，而后者取决于多态性的信息性。
Objective: To develop and compare two new technologies for diagnosing a contiguous gene syndrome, the Williams-Beuren syndrome (WBS).Methods: The first proposed method, named paralogous sequence quantification (PSQ), is based on the use of paralogous sequences located on different chromosomes and quantification of specific mismatches present at these loci using pyrosequencing technology. The second exploits quantitative real time polymerase chain reaction (QPCR) to assess the relative quantity of an analysed locus.Results: A correct and unambiguous diagnosis was obtained for 100% of the analysed samples with either technique (n=165 and n=155, respectively). These methods allowed the identification of two patients with atypical deletions in a cohort of 182 WBS patients. Both patients presented with mild facial anomalies, mild mental retardation with impaired visuospatial cognition, supravalvar aortic stenosis, and normal growth indices. These observations are consistent with the involvement of GTF2IRD1 or GTF2I in some of the WBS facial features.Conclusions: Both PSQ and QPCR are robust, easy to interpret, and simple to set up. They represent a competitive alternative for the diagnosis of segmental aneuploidies in clinical laboratories. They have advantages over fluorescence in situ hybridisation or microsatellites/SNP genotyping for detecting short segmental aneuploidies as the former is costly and labour intensive while the latter depends on the informativeness of the polymorphisms.