TY - JOUR T1 - Two high throughput technologies to detect segmental aneuploidies identify new Williams-Beuren syndrome patients with atypical deletions JF - Journal of Medical Genetics JO - J Med Genet SP - 266 LP - 273 DO - 10.1136/jmg.2005.034009 VL - 43 IS - 3 AU - C Howald AU - G Merla AU - M C Digilio AU - S Amenta AU - R Lyle AU - S Deutsch AU - U Choudhury AU - A Bottani AU - S E Antonarakis AU - H Fryssira AU - B Dallapiccola AU - A Reymond Y1 - 2006/03/01 UR - http://jmg.bmj.com/content/43/3/266.abstract N2 - 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 (nā€Š=ā€Š165 and nā€Š=ā€Š155, 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. ER -