Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services

• Published in: Gene Vol. 535; no. 1; pp. 70 - 78
• Main Authors: Roberts, Jennifer L., Hovanes, Karine, Dasouki, Majed, Manzardo, Ann M., Butler, Merlin G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2014
• Subjects: Adolescent; Adult; autism; Autism spectrum disorders (ASD); Child; Child Development Disorders, Pervasive - genetics; Child, Preschool; Chromosomal microarray analysis; Chromosome Aberrations; chromosomes; Copy number variant (CNV); Developmental delay; Female; females; Genetic Services; genome; Humans; Infant; learning; Learning Disabilities - genetics; Learning disability; Male; males; Microarray Analysis; microarray technology; Middle Aged; oligonucleotides; patients; seizures; Young Adult; YWHAE; PTEN; Developmental delay; PARK2; EEF1B2; ACOXL; ACADL; Learning disability; ZNF407; SACS; POLG; LINS; USP6; EEG; ADIPOQ; COBL; PTH2R; SUMF1; HAX1; MYL1; IL1RAPL1; NDUFS1; SHANK3; HDAC; NLGN2; ANKRD11; CHRNA7; NRXN1; RPE; MRPL19; ITPR1; Chromosomal microarray analysis; XIAP; Autism spectrum disorders (ASD); CNV; FBXO45; CACNA1C; PRPF8; aCGH; FAM117B; KNG1; SD; ASD; BCL2L11; FXR2; ANOVA; MAP2; GALR1; LMNA; NPHP1; SHOX; A2BP1; MBP; PAK2; SH2B1; TRAPPC2; Copy number variant (CNV); BAC; FZD5; IDH1; GATAD2B; SMARCA4; ALS2CR8; CT; KLF7; DLG1; STAG2; DLG4; DNA; FAT1; FISH; PMP22; UCSC; GZF1; ataxin 2-binding protein 1 gene; inositol 1,4,5-triphosphate receptor, type 1 gene; lamin A gene; neurexin 1 gene; frizzled 5 gene; histone deacetylase gene; parathyroid hormone receptor 2 gene; calcium channel, voltage dependent, L-type, alpha 1C subunit gene; acyl-coA dehydrogenase, long chain gene; GATA zinc finger domain-containing protein 2B gene; GDNF-inducible zinc finger protein 1 gene; SH3 and multiple ankyrin repeat domains 3 gene; tracking protein particle complex, subunit 2 gene; polymerase gamma gene; kininogen 1 gene; interleukin 1 receptor accessory protein-like 1 gene; fluorescence in situ hybridization; array comparative genomic hybridization; microtubule-associated protein 2 gene; X-linked inhibitor of apoptosis gene; F-box only 45 gene; ribulose 5-phosphate 3-epimerase gene; discs, large homolog 1 gene; copy number variant; stromal antigen 2 gene; family with sequence similarity 117, member B gene; phosphatase and tensin homolog gene; SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member gene; ubiquitin-specific protease 6 gene; bacterial artificial chromosome; zinc finger protein 407 gene; discs, large homolog 4 gene; NADH-ubiquinone oxidoreductase Fe-S protein 1 gene; sacsin gene; cordon-bleu gene; ankyrin repeat domain-containing protein 11 gene; FAT tumor suppressor 1 gene; sulfatase-modifying factor 1 gene; parkin gene; precursor mRNA-processing factor 8 gene; protein-activated kinase 2 gene; eukaryotic translation elongation factor 1, beta-2 gene; nephrocystin 1 gene; cholinergic receptor, neuronal nicotinic, alpha polypeptide 7 gene; isocitrate dehydrogenase 1 gene; galanin receptor 1 gene; BCL2-like 11 gene; autism spectrum disorder; lines homolog gene; kruppel-like factor 7 gene; electroencephalogram; short stature homeobox gene; myelin basic protein gene; acyl-coA oxidase-like gene; neuroligin 2 gene; standard deviation; ALS2 chromosome region gene 8; myosin, light peptide 1 gene; analysis of variance; deoxyribonucleic acid; HCLS1-associated protein X1 gene; mitochondrial ribosomal protein L19 gene; computed tomography; University of California, Santa Cruz; fragile X mental retardation, autosomal homolog 2 gene; peripheral myelin protein 22 gene; adipocyte-, C1q-, and collagen domain containing gene; SH2B adaptor protein 1 gene; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon isoform gene
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2013.10.020

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 105K 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 4years (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. •Chromosome microarray analysis was performed for autism and learning disability.•Abnormal results were seen in 1 in 5 subjects with autism or learning disability.•Selected genes and chromosome regions of interest are discussed.•Most common microarray abnormality in autism involved chromosome 15q11-q13 region.