title: Genome wide array-CGH and qPCR analysis for the identification of genome defects in Williams' syndrome patients in Saudi Arabia.
abstract: BACKGROUND
  Williams-Beuren Syndrome (WBS) is a rare neurodevelopmental disorder characterized by dysmorphic features, cardiovascular defects, cognitive deficits and developmental delay. WBS is caused by a segmental aneuploidy of chromosome 7 due to heterozygous deletion of contiguous genes at the long arm of chromosome 7q11.23. We aimed to apply array-CGH technique for the detection of copy number variants in suspected WBS patients and to determine the size of the deleted segment at chromosome 7q11.23 in correlation with the phenotype. The study included 24 patients referred to the CEGMR with the provisional diagnosis of WBS and 8 parents. The patients were subjected to conventional Cytogenetic (G-banding) analysis, Molecular Cytogenetic (Fluorescent In-Situ Hybridization), array-based Comparative Genomic Hybridization (array-CGH) and quantitative Real time PCR (qPCR) Techniques.
  
  
  RESULTS
  No deletions were detected by Karyotyping, however, one patient showed unbalanced translocation between chromosome 18 and 19, the karyotype was 45,XX, der(19) t(18;19)(q11.1;p13.3)-18. FISH technique could detect microdeletion in chromosome 7q11.23 in 10/24 patients. Array-CGH and qPCR confirmed the deletion in all samples, and could detect duplication of 7q11.23 in three patients and two parents. Furthermore, the size of the deletion could be detected accurately by both array-CGH and qPCR techniques. Three patients not showing the 7q11.23 deletion were diagnosed by array-CGH to have deletion in chr9p13.1-p11.2, chr18p11.32-p11.21 and chr1p36.13.
  
  
  CONCLUSIONS
  Both FISH and array-CGH are reliable methods for the diagnosis of WBS; however, array-CGH has the advantage of detection of genome deletions/ duplications that cannot otherwise be detected by conventional cytogenetic techniques. Array-CGH and qPCR are useful for detection of deletion sizes and prediction of the interrupted genes and their impact on the disease phenotype. Further investigations are needed for studying the impact of deletion sizes and function of the deleted genes on chromosome 7q11.23.
  
  
  BACKGROUND
  ISRCTN ISRCTN73824458. MOCY-D-16-00041R1. Registered 28 September 2014. Retrospectively registered.
authors.affiliation: Centre of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, 21589 KSA Saudi Arabia.
authors.forename: I R
authors.initials: IR
authors.lastname: Hussein
authors.affiliation: Diagnostic Genomic Medicine Unit (DGMU), King Abdulaziz University, Jeddah, KSA Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Magbooli
authors.affiliation: Faculty of Science, King Abdulaziz University, Jeddah, KSA Saudi Arabia.
authors.forename: E
authors.initials: E
authors.lastname: Huwait
authors.affiliation: Centre of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, 21589 KSA Saudi Arabia.|Faculty of Medical Sciences, King Abdulaziz University, Jeddah, KSA Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Chaudhary
authors.affiliation: Pediatric Cardiology Department, King Abdulaziz University, Jeddah, KSA Saudi Arabia.
authors.forename: R
authors.initials: R
authors.lastname: Bader
authors.affiliation: Centre of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, 21589 KSA Saudi Arabia.|Faculty of Medical Sciences, King Abdulaziz University, Jeddah, KSA Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Gari
authors.affiliation: Centre of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, 21589 KSA Saudi Arabia.
authors.forename: F
authors.initials: F
authors.lastname: Ashgan
authors.affiliation: Centre of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, 21589 KSA Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Alquaiti
authors.affiliation: Centre of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, 21589 KSA Saudi Arabia.|Faculty of Medical Sciences, King Abdulaziz University, Jeddah, KSA Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Abuzenadah
authors.affiliation: Centre of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, 21589 KSA Saudi Arabia.|Diagnostic Genomic Medicine Unit (DGMU), King Abdulaziz University, Jeddah, KSA Saudi Arabia.|Faculty of Medical Sciences, King Abdulaziz University, Jeddah, KSA Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: AlQahtani
keywords: Array-CGH; Congenital heart defects; FISH; Williams Syndrome; qPCR