Genomic Microarrays in Mental Retardation: A Practical Workflow for Diagnostic Applications

被引：112

作者：

Koolen, David A. ^{[1
]}

Pfundt, Rolph ^{[1
]}

de Leeuw, Nicole ^{[1
]}

Hehir-Kwa, Jayne Y. ^{[1
]}

Nillesen, Willy M. ^{[1
]}

Neefs, Ineke ^{[1
]}

Scheltinga, Ine ^{[1
]}

Sistermans, Erik ^{[1
,2
]}

Smeets, Dominique ^{[1
]}

Brunner, Han G. ^{[1
]}

van Kessel, Ad Geurts ^{[1
]}

Veltman, Joris A. ^{[1
]}

de Vries, Bert B. A. ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands

[2] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

来源：

HUMAN MUTATION | 2009年 / 30卷 / 03期

关键词：

array CGH; copy number variation; CNV; intellectual disability; mental retardation; microarray; COPY-NUMBER VARIATION; 15Q24 MICRODELETION SYNDROME; HYBRIDIZATION ARRAY-CGH; CHROMOSOME REARRANGEMENTS; RECOGNIZABLE PHENOTYPE; CONGENITAL-ANOMALIES; DEVELOPMENTAL DELAY; DYSMORPHIC FEATURES; CORPUS-CALLOSUM; CRITICAL REGION;

D O I：

10.1002/humu.20883

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Microarray-based copy number analysis has found its way into routine clinical practice, predominantly for the diagnosis of patients with unexplained mental retardation. However, the clinical interpretation of sub, microscopic copy number variants (CNVs) is complicated by the fact that many CNVs are also present in the general population. Here we introduce and discuss a workflow that can be used in routine diagnostics to assess the clinical significance of the CNVs identified. We applied this scheme to our cohort of 386 individuals with unexplained mental retardation tested using a genome-wide tiling-resolution DNA microarray and to 978 additional patients with mental retardation reported in 15 genome-wide microarray studies extracted from the literature. In our cohort of 386 patients we identified 25 clinically significant copy number losses (median size 2.6 Mb), nine copy number gains (median size 2.0 Mb), and one mosaic numerical chromo, some aberration. Accordingly, the overall diagnostic yield of clinically significant CNVs was 9.1%. Taken together, our cohort and the patients described in the literature include a total of 1,364 analyses of DNA copy number in which a total of 11.2% (71.9% losses, 19.6% gains, 8.5% complex) could be identified, reflecting the overall diagnostic yield of clinically significant CNVs in individuals with unexplained mental retardation. Hum Mutat 30, 283-292, 2009. (C) 2008 Wiley-Liss, Inc.

引用

页码：283 / 292

页数：10

共 57 条

[1] Whole-genome array-CGH identifies novel contiguous gene deletions and duplications associated with developmental delay, mental retardation, and dysmorphic features [J].