¹Center for Human and Clinical Genetics, Department of Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands

Correspondence: Dr CAL Ruivenkamp, Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), Postzone S-6-P, Einthovenweg 20, 2333 CZ Leiden, The Netherlands. Tel: +31 71 526 98 00; Fax: +31 71 526 83 76; E-mail: c.ruivenkamp@lumc.nl

Received 30 January 2009; Revised 9 April 2009; Accepted 9 April 2009; Published online 13 May 2009.

Abstract

High-density single-nucleotide polymorphism (SNP) genotyping technology enables extensive genotyping as well as the detection of increasingly smaller chromosomal aberrations. In this study, we assess molecular karyotyping as first-round analysis of patients with mental retardation and/or multiple congenital abnormalities (MR/MCA). We used different commercially available SNP array platforms, the Affymetrix GeneChip 262K NspI, the Genechip 238K StyI, the Illumina HumanHap 300 and HumanCNV 370 BeadChip, to detect copy number variants (CNVs) in 318 patients with unexplained MR/MCA. We found abnormalities in 22.6% of the patients, including six CNVs that overlap known microdeletion/duplication syndromes, eight CNVs that overlap recently described syndromes, 63 potentially pathogenic CNVs (in 52 patients), four large segments of homozygosity and two mosaic trisomies for an entire chromosome. This study shows that high-density SNP array analysis reveals a much higher diagnostic yield as that of conventional karyotyping. SNP arrays have the potential to detect CNVs, mosaics, uniparental disomies and loss of heterozygosity in one experiment. We, therefore, propose a novel diagnostic approach to all MR/MCA patients by first analyzing every patient with an SNP array instead of conventional karyotyping.