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Two high throughput technologies to detect segmental aneuploidies identify new Williams-Beuren syndrome patients with atypical deletions
  1. C Howald1,*,
  2. G Merla1,*,
  3. M C Digilio3,
  4. S Amenta4,
  5. R Lyle1,
  6. S Deutsch1,
  7. U Choudhury5,
  8. A Bottani6,
  9. S E Antonarakis5,
  10. H Fryssira4,
  11. B Dallapiccola2,
  12. A Reymond7
  1. 1Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
  2. 2CSS-Mendel Institute, Roma, Italy
  3. 3Medical Genetics Unit, IRCCS “Bambino Gesù” Hospital, Rome, Italy
  4. 4Department of Medical Genetics, Athens University School of Medicine, Aghia Sofia Children’s Hospital, Athens, Greece
  5. 5Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
  6. 6Division of Medical Genetics, Geneva University Hospitals, Geneva, Switzerland
  7. 7Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
  1. Correspondence to:
 Alexandre Reymond
 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland; alexandre.reymond{at}


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.

  • FISH, fluorescence in situ hybridisation
  • LCR, low copy repeat
  • PSM, paralogous sequence mismatch
  • PSQ, paralogous sequence quantification
  • QPCR, quantitative real time polymerase chain reaction
  • SNP, single nucleotide polymorphism
  • WBS, Williams-Beuren syndrome
  • Williams-Beuren syndrome
  • aneuploidy
  • genomics
  • real time PCR
  • pyrosequencing

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  • * These authors contributed equally to this work

  • Published Online First 1 July 2005

  • Conflicts of interest: none declared