A novel deletion in proximal 22q associated with cardiac septal defects and microcephaly: a case report

Caroline Ogilvie,Roland G Roberts,Frances Flinter,Joo Ahn,Kathy Mann

doi:10.1186/1755-8166-2-9

Caroline Ogilvie, Roland G Roberts + Show 3 more

Open Access

https://doi.org/10.1186/1755-8166-2-9

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Abstract

BackgroundProximal 22q is rich in low copy repeats (LCRs) which mediate non-allelic homologous recombination and give rise to deletions and duplications of varying size depending on which LCRs are involved.MethodsA child with multiple septal defects and other congenital anomalies was investigated for genome imbalance using multiplex ligation-dependent probe amplification (MLPA) for subtelomeres and microdeletion loci, followed by array comparative genomic hybridization (CGH) using oligonucleotide arrays with 44,000 probes across the genome.ResultsMLPA identified a single probe deletion in the SNAP29 gene within band 22q11.21. Follow-up array CGH testing revealed a ~1.4-Mb deletion from 19,405,375 bp to 20,797,502 bp, encompassing 28 genes.ConclusionThis deletion is likely to be causally associated with the proband's congenital anomalies. Previous publications describing deletions in proximal 22q have reported deletions between LCRs 1 to 4, associated with 22q11 deletion syndrome; in addition, deletions between LCRs 4 and 6 have been described associated with "distal 22q11 deletion syndrome". To our knowledge, this is the first deletion which spans LCR4 and is not apparently mediated by LCRs. Comparison of the phenotypes found in conjunction with previously reported deletions, together with the function and expression patterns of genes in the deleted region reported here, suggests that haploinsufficiency for the Crk-like (CRKL) gene may be responsible for the reported cardiac abnormalities.

Highlights

Proximal 22q is rich in low copy repeats (LCRs) which mediate non-allelic homologous recombination and give rise to deletions and duplications of varying size depending on which LCRs are involved
The proximal region of the chromosome 22 long arm is rich in low copy repeats (LCRs), which are known to mediate non-allelic homologous recombination (NAHR)[1]
In this paper we describe a patient with an atypical deletion spanning LCR4, and compare her features with those found in overlapping deletions

Summary

Introduction

Proximal 22q is rich in low copy repeats (LCRs) which mediate non-allelic homologous recombination and give rise to deletions and duplications of varying size depending on which LCRs are involved. The proximal region of the chromosome 22 long arm is rich in low copy repeats (LCRs), which are known to mediate non-allelic homologous recombination (NAHR)[1]. The most common of these events is the recombination between LCRs 2 and 4, which gives rise to a 3-megabase (Mb) deletion, associated with chromosome 22q11 deletion syndrome (which includes features of Velocardiofacial syndrome and DiGeorge syndrome)[2]. Molecular Cytogenetics 2009, 2:9 http://www.molecularcytogenetics.org/content/2/1/9 milder but similar features[3,4]. Until recently, these reciprocal events were thought to be underdetected, as theoretically they should occur at the same frequency as the deletion. The 1.5-Mb deletion that occurs following NAHR between LCRs 2 and 3 is associated with similar features to those found in individuals with the 3-Mb deletion[6]

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