Submicroscopic deletions and duplications in individuals with intellectual disability detected by array‐CGH

Abstract

Intellectual disability (ID) affects about 3% of the population (IQ < 70), and in about 40% of moderate (IQ 35-49) to severe ID (IQ < 34), and 70% of cases of mild ID (IQ 50-70), the etiology of the disease remains unknown. It has long been suspected that chromosomal gains and losses undetectable by routine cytogenetic analysis (i.e., less than 5-10 Mb in size) are implicated in ID of unknown etiology. Array CGH has recently been used to perform a genome-wide screen for submicroscopic gains and losses in individuals with a normal karyotype but with features suggestive of a chromosome abnormality. In two recent studies, the technique has demonstrated a approximately 15% detection rate for de novo copy number changes of individual clones or groups of clones. Here, we describe a study of 22 individuals with mild to moderate ID and nonsyndromic pattern of dysmorphic features suspicious of an underlying chromosome abnormality, using the 3 Mb and 1 Mb commercial arrays (Spectral Genomics). Deletions and duplications of 16 clones, previously described to show copy number variability in normal individuals [Iafrate et al., 2004; Lapierre et al., 2004; Schoumans et al., 2004; Vermeesch et al., 2005] were seen in 21/22 subjects and were considered polymorphisms. In addition, three subjects showed submicroscopic deletions and duplications not previously reported as normal variants. Two of these submicroscopic changes were of de novo origin (microdeletions at 7q36.3 and a microduplication at 11q12.3-13.1) and one was of unknown origin as parental testing of origin could not be performed (microduplication of Xp22.3). The clinical description of the three subjects with submicroscopic chromosomal changes at 7q36.3, 11q12.3-13.1, Xp22.3 is provided.

Genetic testing in autism: how much is enough?

“…Currently, commercial arrays target selected regions of the genome, including the subtelomeres and known deletions and duplications that are associated with genetic syndromes. 23,55,56 With the advent of arrays with genome-wide coverage, it is likely that additional small cryptic genomic rearrangements will be identified in some ASD patients. Indeed, Jacquemot et al 57 identified "clinically relevant" genomic rearrangements in 8/29 (27.5%) patients with "syndromic" ASDs using a large insert clone (BAC or PAC) array developed at the Wellcome Trust Sanger Institute with a resolution of 1 Mb.…”

Segmental Copy‐Number Variation Observed in Japanese by Array‐CGH

“…The results from those studies (Gimelli et al 2003;Tyson et al 2005) showed that the number of CNVs (assumed not to be directly relevant to human genetic disease) was also much smaller than the number of CNVs observed in the other studies (Iafrate et al 2004;Redon et al 2006;Wong et al 2007). …”

2p15–p16.1 microdeletion syndrome: molecular characterization and association of the OTX1 and XPO1 genes with autism spectrum disorders

“…24,25 Tag SNP selection and genotyping Eight Tag SNPs for XPO1 and three Tag SNPs in OTX1 and its flanking region (Supplementary Table 2) were selected based on Hapmap information, using the Applied Biosystems' SNP Browser (www.appliedbiosystems.com) and criteria as previously described. 26 Genotyping of the Tag SNPs was carried out using validated TaqMan SNP assays (Applied Biosystems) as previously described.…”