Prevalence of selected genomic deletions and duplications in a French–Canadian population‐based sample of newborns

Abstract

Chromosomal microarray analysis has identified many novel microdeletions or microduplications that produce neurodevelopmental disorders with a recognizable clinical phenotype and that are not observed in normal individuals. However, imbalance of other genomic regions is associated with a variable phenotype with intellectual disability (ID) or autism in some individuals but are also observed in completely normal individuals. Several large studies have reported the prevalence of copy number (CN) variants in people with particular features (e.g., ID, autism, schizophrenia, or epilepsy); few studies have investigated the prevalence of genomic CN changes in the general population. We used a high-throughput method to screen 6813 consecutive cord blood samples from a predominantly French–Canadian population to assess genomic CN in five genomic regions: 1p36, 15q11-q13, 16p11.2, 16p11.2-p12.2, and 22q11.2. We identified one deletion and one duplication within 1p36, two deletions of 15q11-q13, eight deletions of 16p11.2-p12.2, two deletions and five duplications of 16p11.2, and six duplications of 22q11.2. This study provides estimates of the frequency of CN variants in an unselected population. Our findings have important implications for genetic counseling.

Murine model indicates 22q11.2 signaling adaptor CRKL is a dosage-sensitive regulator of genitourinary development

“…An aCGH and CNV qPCR screen showed duplications (n = 2) and deletions (n = 2) encompassing CRKL (Fig. 1, "Lamb Lab Patients") were enriched in a population of GU-abnormal patients and present at 1.4% (n = 277; P = 0.0004) compared with the unselected general population where CRKL-encompassing CNVs are present at 0.088% (6 of 6,813; only duplications found) (19). CNVs in CRKL are also enriched in our cohort of GU-abnormal patients compared with rates in the generally disease-enriched cohort of the ExAC database (19 deletions; 47 duplications; 66 of 60,706; 0.1%; all analyzed ethnic subgroups represented; P = 0.03).…”

Cross-Disorder Comparison of Four Neuropsychiatric CNV Loci

“…1a), however, the association with neuropsychiatric disorders was only demonstrated in 2008 [15][16][17]54]. The deletion is observed in 1 in 3,500 live births [55] and was initially described as a cause of idiopathic ASD. Subsequently, it has been identified in ID [56], schizophrenia [18], and a host of other neuropsychiatric conditions.…”

“…Subsequently, it has been identified in ID [56], schizophrenia [18], and a host of other neuropsychiatric conditions. As [55]. Like the 16p11.2 deletions, they were initially detected in individuals with idiopathic ASD [15,17], but subsequently this CNV has been associated with many neurodevelopmental disorders including ID, speech delay, epilepsy, bipolar disorder, schizophrenia, ADHD, anxiety disorder, motor delay, and spastic quadriparesis [18,56,58].…”

Behavioral abnormalities are common and severe in patients with distal 22q11.2 microdeletions and microduplications

“…The frequency of the reciprocal microduplication is unclear at present (Tucker et al. 2013). Both the duplication and the deletion are facilitated by LCRs in 22q11.2, labeled LCR22 A–D from centromere to telomere (alternatively the LCRs are numbered).…”

“…The most commonly occurring microdeletion is proximal microdeletion 22q11.2 or DiGeorge/velocardiofacial syndrome, present in about 1 in 2000-6000 live births (Wilson et al 1994). The frequency of the reciprocal microduplication is unclear at present (Tucker et al 2013). Both the duplication and the deletion are facilitated by LCRs in 22q11.2, labeled LCR22 A-D from centromere to telomere (alternatively the LCRs are numbered).…”