Array CGH analysis of a cohort of Russian patients with intellectual disability

Abstract

The use of array comparative genomic hybridization (array CGH) as a diagnostic tool in molecular genetics has facilitated the identification of many new microdeletion/microduplication syndromes (MMSs). Furthermore, this method has allowed for the identification of copy number variations (CNVs) whose pathogenic role has yet to be uncovered. Here, we report on our application of array CGH for the identification of pathogenic CNVs in 79 Russian children with intellectual disability (ID). Twenty-six pathogenic or likely pathogenic changes in copy number were detected in 22 patients (28%): 8 CNVs corresponded to known MMSs, and 17 were not associated with previously described syndromes. In this report, we describe our findings and comment on genes potentially associated with ID that are located within the CNV regions.

Keywords: ABLIM3; ACAD10; ADHD; AFAP1L1; AGA; ASTN1; Array comparative genomic hybridization (array CGH); CASP3; CGH; CHERISH; CNS; CNTN6; CNV; Copy number variation (CNV); DDX10; DEAD (Asp-Glu-Ala-Asp) box polypeptide 10; DECIPHER; EEG; EU; European Union; FJX1; GLRA3; HAND2; HFE; ID; IFN; IL17B; ING2; IQ; IRF1; IRF2; Intellectual disability; LDLRAD3; METTL4; MMP14; MMSs; MRI; NDC80; NDC80 kinetochore complex component; NEIL3; NO; OMIM; PCR; PL CNS; PON1; PON2; PON3; SBF; SCGN; SCRG1; SET domain binding factor; SLC1A2; SLC5A7; SLC7A7; SMCHD1; SUFU; SWAP switching B-cell complex 70kDa subunit; SWAP70; Ski-related novel protein N; SnoN; TGFβ; TNR; TRIM44; WAGR; Wilms tumor, aniridia, genitourinary anomalies and mental retardation syndrome; actin binding LIM protein family, member 3; actin filament associated protein 1-like 1; acyl-CoA dehydrogenase family, member 10; aspartylglucosaminidase; astrotactin 1; attention-deficit hyperactivity disorder; caspase 3, apoptosis-related cysteine peptidase; central nervous system; comparative genomic hybridization; contactin 6; copy number variation; database of chromosomal imbalance and phenotype in humans using ensembl resources; electroencephalogram; four jointed box 1 (Drosophila); glycine receptor, alpha 3; grant of European Community's Seventh Framework Programme; heart and neural crest derivatives expressed 2; hemochromatosis; inhibitor of growth family, member 2; intellectual disability; intelligence quotient; interferon; interferon regulatory factor 1; interferon regulatory factor 2; interleukin 17B; low density lipoprotein receptor class A domain containing 3; magnetic resonance imaging; matrix metallopeptidase 14 (membrane-inserted); methyltransferase like 4; microdeletion/microduplication syndromes; nei endonuclease VIII-like 3 (E. coli); nitrogen oxide; online mendelian inheritance in man; paraoxonase 1; paraoxonase 2; paraoxonase 3; perinatal lesion of central nervous system; polymerase chain reaction; qPCR; quantitative PCR; secretagogin, EF-hand calcium binding protein; solute carrier family 1 (glial high affinity glutamate transporter), member 2; solute carrier family 5 (sodium/choline cotransporter), member 7; solute carrier family 7 (amino acid transporter light chain, y+L system), member 7; stimulator of chondrogenesis 1; structural maintenance of chromosomes flexible hinge domain containing 1; suppressor of fused homolog (Drosophila); tenascin R; transforming growth factor beta; tripartite motif containing 44.