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High‐Resolution genomic arrays identify CNVs that phenocopy the chromosome 22q11.2 deletion syndrome
Author(s) -
Busse Tracy,
Graham John M.,
Feldman Gerald,
Perin Juan,
Catherwood Anne,
Knowlton Robert,
Rappaport Eric F.,
Emanuel Beverly,
Driscoll Deborah A.,
Saitta Sulagna C.
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21395
Subject(s) - digeorge syndrome , biology , copy number variation , genetics , gene duplication , snp array , comparative genomic hybridization , phenocopy , microarray , chromosome , microdeletion syndrome , phenotype , single nucleotide polymorphism , gene , genome , genotype , gene expression
The 22q11 Deletion Syndrome includes the overlapping phenotypes of DiGeorge/Velocardiofacial Syndromes, characterized by conotruncal heart defects, cleft palate, thymus, and parathyroid gland dysplasia. The majority (90%) of patients harbor detectable chr22q11.2 deletions, but a genetic etiology for the remainder of patients without a deletion can remain undefined despite major birth defects. We analyzed DNA from eight patients with normal 22q11 FISH studies by high‐density single nucleotide polymorphism (SNP) arrays and identified potentially pathogenic copy number variants (CNVs) in four of eight patients. Two patients showed large CNVs in regions of known genomic disorders: one a deletion of distal chr22q11.2 and the other a duplication of chr5q35. A 3‐Mb deletion of chr19p13.3 that includes a gene associated with conotruncal heart defects was found in a third patient. Two potentially pathogenic CNVs were found in a fourth patient: a large heterozygous deletion of chr6p24 and a smaller duplication of chr9p24. Our findings support a recent consensus statement advocating chromosomal microarray analysis as a first‐line diagnostic approach for patients with multiple congenital anomalies. In patients with phenotypes suggestive of the 22q11.2 syndrome spectrum and normal FISH, microarray analysis can uncover the molecular basis of other genomic disorders whose features overlap those of 22q11.2 deletions.Hum Mutat 31:1–7, 2010. © 2010 Wiley‐Liss, Inc.