A Novel Deletion in Proximal 22q Associated with Cardiac Septal Defects and Microcephaly: a Case Report

Overview

Journal Mol Cytogenet

Publisher Biomed Central

Specialty Biochemistry

Date 2009 Feb 26

PMID 19239688

Citations 4

Authors

Caroline Mackie Ogilvie

Joo Wook Ahn

Kathy Mann

Roland G Roberts

Frances Flinter

Affiliations

Soon will be listed here.

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.

Citing Articles

22q11.21 Deletions: A Review on the Interval Mediated by Low-Copy Repeats C and D.

Bertini V, Cambi F, Legitimo A, Costagliola G, Consolini R, Valetto A Genes (Basel). 2025; 16(1).

PMID: 39858619 PMC: 11764475. DOI: 10.3390/genes16010072.

A mouse splice-site mutant and individuals with atypical chromosome 22q11.2 deletions demonstrate the crucial role for crkl in craniofacial and pharyngeal development.

Miller K, Tan T, Welfare M, White S, Stark Z, Savarirayan R Mol Syndromol. 2015; 5(6):276-86.

PMID: 25565927 PMC: 4281577. DOI: 10.1159/000368865.

Mapping the deletion endpoints in individuals with 22q11.2 deletion syndrome by droplet digital PCR.

Hwang V, Maar D, Regan J, Angkustsiri K, Simon T, Tassone F BMC Med Genet. 2014; 15:106.

PMID: 25312060 PMC: 4258952. DOI: 10.1186/s12881-014-0106-5.

22q11.2 Distal Deletion Syndrome: Description of a New Case with Truncus Arteriosus Type 2 and Review.

Garavelli L, Rosato S, Wischmeijer A, Gelmini C, Esposito A, Mazzanti L Mol Syndromol. 2012; 2(1):35-44.

PMID: 22582037 PMC: 3343753. DOI: 10.1159/000334262.

Essential roles of snap-29 in C. elegans.

Kang J, Bai Z, Zegarek M, Grant B, Lee J Dev Biol. 2011; 355(1):77-88.

PMID: 21545795 PMC: 3118655. DOI: 10.1016/j.ydbio.2011.04.013.

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