Case report

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

Caroline Mackie Ogilvie¹ , Joo Wook Ahn¹ , Kathy Mann¹ , Roland G Roberts² and Frances Flinter³

¹  Cytogenetics Department, Guy's & St Thomas' NHS Foundation Trust, London, UK

²  Department of Medical & Molecular Genetics, King's College London School of Medicine, London, UK

³  Genetics Department, Guy's & St Thomas' NHS Foundation Trust, London, UK

author email corresponding author email

Molecular Cytogenetics 2009, 2:9doi:10.1186/1755-8166-2-9

Published:	24 February 2009

Abstract

Background

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.

Methods

A 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.

Results

MLPA 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.

Conclusion

This 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.