Distal 22q11.2 microduplication encompassing the BCR gene

Abstract

Chromosome 22 band q11.2 has been recognized to be highly susceptible to subtle microdeletions and microduplications, which have been attributed to the presence of several large segmental duplications; also known as low copy repeats (LCRs). These LCRs function as mediators of non-allelic homologous recombination (NAHR), which results in these chromosomal rearrangements as a result of unequal crossover. The four centromeric LCRs at proximal 22q11.2 have been previously implicated in recurrent chromosomal rearrangements including the DiGeorge/Velocardiofacial syndrome (DG/VCFs) microdeletion and its reciprocal microduplication. Recently, we and others have demonstrated that the four telomeric LCRs at distal 22q11.2 are causally implicated in a newly recognized recurrent distal 22q11.2 microdeletion syndrome in the region immediately telomeric to the DG/VCFs typically deleted region. Here we report on the clinical, cytogenetic, and array CGH studies of a 4.5-year-old girl with history of failure to thrive, developmental delay (DD), and relative macrocephaly. She carries a paternally inherited approximately 2.1 Mb microduplication at distal 22q11.2, which spans approximately 34 annotated genes, and is flanked by two of the four telomeric 22q11.2 LCRs. We conclude that the four telomeric LCRs at distal 22q11.2 can mediate both deletions and duplications in this genomic region. Both deletions and duplication of this region present with subtle clinical features including mild to moderate mental retardation, DD, and mild dysmorphic features.

An atypical 0.73 MB microduplication of 22q11.21 and a novel SALL4 missense mutation associated with thumb agenesis and radioulnar synostosis

“…The major phenotypic features of these patients are developmental/speech delay, behavioral problems, mild dysmorphic facial features, hearing loss, and growth delay, but may be highly variable [Portnoï et al, 2009]. In addition to these more common microduplications, atypical microduplications have been identified between LCR-B and LCR-D, extending beyond LCR-D, and entirely distal to LCR-D [Ensenauer et al, 2003;Fan et al, 2007;Descartes et al, 2008;Ou et al, 2008;Coppinger et al, 2009;Pebrel-Richard et al, 2012].…”

A de novo 22q11.22q11.23 interchromosomal tandem duplication in a boy with developmental delay, hyperactivity, and epilepsy

“…Recently, many patients with distal 22q11.2 microduplications have been reported [Ensenauer et al, 2003;Descartes et al, 2008;Ou et al, 2008;Coppinger et al, 2009]. Among them, the detailed clinical manifestations of 15 patients are summarized in Table I.…”

Identification of Copy Number Variants on Human Chromosome 22 in Patients with a Variety of Clinical Findings

“…In addition to these defined genomic disorders, other pathogenic copy number variants (CNVs) and CNVs of unknown clinical CNVs on Human Chromosome 22 Cytogenet Genome Res 2011;134:260-268 261 significance have been identified [Descartes et al, 2008;Brunet et al, 2009;Coppinger et al, 2009;Foley et al, 2009;Abo-Dalo et al, 2010], while numerous genomic imbalances are documented as benign CNVs without apparent clinical significance (http://projects.tcag.ca/variation).…”