title: Identification of subtelomeric genomic imbalances and breakpoint mapping with quantitative PCR in 296 individuals with congenital defects and/or mental retardation.
abstract: BACKGROUND
  Submicroscopic imbalances in the subtelomeric regions of the chromosomes are considered to play an important role in the aetiology of mental retardation (MR). The aim of the study was to evaluate a quantitative PCR (qPCR) protocol established by Boehm et al. (2004) in the clinical routine of subtelomeric testing.
  
  
  RESULTS
  296 patients with MR and a normal karyotype (500-550 bands) were screened for subtelomeric imbalances by using qPCR combined with SYBR green detection. In total, 17 patients (5.8%) with 20 subtelomeric imbalances were identified. Six of the aberrations (2%) were classified as causative for the symptoms, because they occurred either de novo in the patients (5 cases) or the aberration were be detected in the patient and an equally affected parent (1 case). The extent of the deletions ranged from 1.8 to approximately 10 Mb, duplications were 1.8 to approximately 5 Mb in size. In 6 patients, the copy number variations (CNVs) were rated as benign polymorphisms, and the clinical relevance of these CNVs remains unclear in 5 patients (1.7%). Therefore, the overall frequency of clinically relevant imbalances ranges between 2% and 3.7% in our cohort.
  
  
  CONCLUSIONS
  This study illustrates that the qPCR/SYBR green technique represents a rapid and versatile method for the detection of subtelomeric imbalances and the option to map the breakpoint. Thus, this technique is highly suitable for genotype/phenotype studies in patients with MR/developmental delay and/or congenital defects.
authors.affiliation: Institute of Human Genetics, Georg August University, Göttingen, Germany. ibartel@gwdg.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Auber
authors.forename: Verena
authors.initials: V
authors.lastname: Bruemmer
authors.forename: Barbara
authors.initials: B
authors.lastname: Zoll
authors.forename: Peter
authors.initials: P
authors.lastname: Burfeind
authors.forename: Detlef
authors.initials: D
authors.lastname: Boehm
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.forename: Knut
authors.initials: K
authors.lastname: Brockmann
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Wilichowski
authors.forename: Loukas
authors.initials: L
authors.lastname: Argyriou
authors.forename: Iris
authors.initials: I
authors.lastname: Bartels