Chromosomal microarray analysis is now commonly used in clinical practice to identify copy number variants (CNVs) in the human genome. We report our experience with the use of the 105 K and 180K oligonucleotide microarrays in 215 consecutive patients referred with either autism or autism spectrum disorders (ASD) or developmental delay/learning disability for genetic services at the University of Kansas Medical Center during the past 4 years (2009-2012). Of the 215 patients [140 males and 75 females (male/female ratio=1.87); 65 with ASD and 150 with learning disability], abnormal microarray results were seen in 45 individuals (21%) with a total of 49 CNVs. Of these findings, 32 represented a known diagnostic CNV contributing to the clinical presentation and 17 represented non-diagnostic CNVs (variants of unknown significance). Thirteen patients with ASD had a total of 14 CNVs, 6 CNVs recognized as diagnostic and 8 as non-diagnostic. The most common chromosome involved in the ASD group was chromosome 15. For those with a learning disability, 32 patients had a total of 35 CNVs. Twenty-six of the 35 CNVs were classified as a known diagnostic CNV, usually a deletion (n=20). Nine CNVs were classified as an unknown non-diagnostic CNV, usually a duplication (n=8). For the learning disability subgroup, chromosomes 2 and 22 were most involved. Thirteen out of 65 patients (20%) with ASD had a CNV compared with 32 out of 150 patients (21%) with a learning disability. The frequency of chromosomal microarray abnormalities compared by subject group or gender was not statistically different. A higher percentage of individuals with a learning disability had clinical findings of seizures, dysmorphic features and microcephaly, but not statistically significant. While both groups contained more males than females, a significantly higher percentage of males were present in the ASD group.
Keywords: A2BP1; ACADL; ACOXL; ADIPOQ; ALS2 chromosome region gene 8; ALS2CR8; ANKRD11; ANOVA; ASD; Autism spectrum disorders (ASD); BAC; BCL2-like 11 gene; BCL2L11; CACNA1C; CHRNA7; CNV; COBL; CT; Chromosomal microarray analysis; Copy number variant (CNV); DLG1; DLG4; DNA; Developmental delay; EEF1B2; EEG; F-box only 45 gene; FAM117B; FAT tumor suppressor 1 gene; FAT1; FBXO45; FISH; FXR2; FZD5; GALR1; GATA zinc finger domain-containing protein 2B gene; GATAD2B; GDNF-inducible zinc finger protein 1 gene; GZF1; HAX1; HCLS1-associated protein X1 gene; HDAC; IDH1; IL1RAPL1; ITPR1; KLF7; KNG1; LINS; LMNA; Learning disability; MAP2; MBP; MRPL19; MYL1; NADH-ubiquinone oxidoreductase Fe-S protein 1 gene; NDUFS1; NLGN2; NPHP1; NRXN1; PAK2; PARK2; PMP22; POLG; PRPF8; PTEN; PTH2R; RPE; SACS; SD; SH2B adaptor protein 1 gene; SH2B1; SH3 and multiple ankyrin repeat domains 3 gene; SHANK3; SHOX; SMARCA4; STAG2; SUMF1; SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member gene; TRAPPC2; UCSC; USP6; University of California, Santa Cruz; X-linked inhibitor of apoptosis gene; XIAP; YWHAE; ZNF407; aCGH; acyl-coA dehydrogenase, long chain gene; acyl-coA oxidase-like gene; adipocyte-, C1q-, and collagen domain containing gene; analysis of variance; ankyrin repeat domain-containing protein 11 gene; array comparative genomic hybridization; ataxin 2-binding protein 1 gene; autism spectrum disorder; bacterial artificial chromosome; calcium channel, voltage dependent, L-type, alpha 1C subunit gene; cholinergic receptor, neuronal nicotinic, alpha polypeptide 7 gene; computed tomography; copy number variant; cordon-bleu gene; deoxyribonucleic acid; discs, large homolog 1 gene; discs, large homolog 4 gene; electroencephalogram; eukaryotic translation elongation factor 1, beta-2 gene; family with sequence similarity 117, member B gene; fluorescence in situ hybridization; fragile X mental retardation, autosomal homolog 2 gene; frizzled 5 gene; galanin receptor 1 gene; histone deacetylase gene; inositol 1,4,5-triphosphate receptor, type 1 gene; interleukin 1 receptor accessory protein-like 1 gene; isocitrate dehydrogenase 1 gene; kininogen 1 gene; kruppel-like factor 7 gene; lamin A gene; lines homolog gene; microtubule-associated protein 2 gene; mitochondrial ribosomal protein L19 gene; myelin basic protein gene; myosin, light peptide 1 gene; nephrocystin 1 gene; neurexin 1 gene; neuroligin 2 gene; parathyroid hormone receptor 2 gene; parkin gene; peripheral myelin protein 22 gene; phosphatase and tensin homolog gene; polymerase gamma gene; precursor mRNA-processing factor 8 gene; protein-activated kinase 2 gene; ribulose 5-phosphate 3-epimerase gene; sacsin gene; short stature homeobox gene; standard deviation; stromal antigen 2 gene; sulfatase-modifying factor 1 gene; tracking protein particle complex, subunit 2 gene; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon isoform gene; ubiquitin-specific protease 6 gene; zinc finger protein 407 gene.
© 2013 Elsevier B.V. All rights reserved.