Research

Identification of subtelomeric genomic imbalances and breakpoint mapping with quantitative PCR in 296 individuals with congenital defects and/or mental retardation

Bernd Auber¹ , Verena Bruemmer¹ , Barbara Zoll¹ , Peter Burfeind¹ , Detlef Boehm² , Thomas Liehr³ , Knut Brockmann⁴ , Ekkehard Wilichowski⁴ , Loukas Argyriou⁵ and Iris Bartels¹

¹  Institute of Human Genetics, Georg August University, Göttingen, Germany

²  Center for Human Genetics, Freiburg, Germany

³  Institute of Human Genetics, University of Jena, Jena, Germany

⁴  Department of Paediatrics and Paediatric Neurology, Georg August University, Göttingen, Germany

⁵  Institute of Human Genetics, University of Lübeck, Lübeck, Germany

author email corresponding author email

Molecular Cytogenetics 2009, 2:10doi:10.1186/1755-8166-2-10

Published:	12 March 2009

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.

Conclusion

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.