A new diagnostic workflow for patients with mental retardation and/or multiple congenital abnormalities: test arrays first

被引:0
作者
Antoinet CJ Gijsbers
Janet YK Lew
Cathy AJ Bosch
Janneke HM Schuurs-Hoeijmakers
Arie van Haeringen
Nicolette S den Hollander
Sarina G Kant
Emilia K Bijlsma
Martijn H Breuning
Egbert Bakker
Claudia AL Ruivenkamp
机构
[1] Center for Human and Clinical Genetics,Department of Clinical Genetics
[2] Leiden University Medical Center (LUMC),undefined
来源
European Journal of Human Genetics | 2009年 / 17卷
关键词
SNP array; mental retardation; copy number variants; diagnostic workflow;
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学科分类号
摘要
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.
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页码:1394 / 1402
页数:8
相关论文
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