Atypical deletions suggest five 22q11.2 critical regions related to the DiGeorge/velo-cardio-facial syndrome

Francesca Amati, Emanuela Conti, Antonio Novelli, Mario Bengala, Maria Cristina Digilio, Bruno Marino, Aldo Giannotti, Orazio Gabrielli, Giuseppe Novelli, Bruno Dallapiccola

Research output: Contribution to journalArticlepeer-review

Abstract

Deletions of chromosome 22q11.2 have been associated with distinct phenotypes including DiGeorge syndrome (DGS) and velo-cardio-facial (VCFS) syndrome. These diseases result from a failure to form derivatives of the third and fourth branchial arches during development. DGS/VCFS deletions usually encompass about 3 Mb of genomic DNA in more than 90% of patients. However, deletion mapping studies have failed to demonstrate the existence of a single small region of overlap (SRO) and ruled out any obvious correlation between site or size of deletion and severity of clinical phenotype. We describe three patients carrying 'atypical' deletions presenting the DGS/VCFS phenotype. A comparative analysis of deletions in our patients and those previously published has suggested the existence of five distinct critical regions within the 22q11.2 locus. This observation argues that DGS/VCFS results from haploinsufficiency secondary to a complex and as yet unexplained molecular mechanism, probably involving chromatin effects in mediating gene expression throughout the entire region.

Original languageEnglish
Pages (from-to)903-909
Number of pages7
JournalEuropean Journal of Human Genetics
Volume7
Issue number8
Publication statusPublished - 1999

Keywords

  • Chromosome 22
  • Deletion map
  • DiGeorge syndrome
  • Velo-cardio-facial syndrome

ASJC Scopus subject areas

  • Genetics(clinical)

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