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.

Amati, F., Conti, E., Novelli, A., Bengala, M., Diglio, M., Marino, B., et al. (1999). Atypical deletions suggest five 22q11.2 critical regions related to the DiGeorge/velo-cardio-facial syndrome. EUROPEAN JOURNAL OF HUMAN GENETICS, 7(8), 903-909 [10.1038/sj.ejhg.5200399].

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

AMATI, FRANCESCA;NOVELLI, GIUSEPPE;
1999-12-01

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.
dic-1999
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/03 - GENETICA MEDICA
English
Con Impact Factor ISI
Child, Preschool; DiGeorge Syndrome; Face; Female; Heart Defects, Congenital; Humans; In Situ Hybridization, Fluorescence; Infant; Intellectual Disability; Karyotyping; Male; Phenotype; Chromosomes, Human, Pair 22; Gene Deletion
http://www.nature.com/ejhg/journal/v7/n8/abs/5200399a.html
Amati, F., Conti, E., Novelli, A., Bengala, M., Diglio, M., Marino, B., et al. (1999). Atypical deletions suggest five 22q11.2 critical regions related to the DiGeorge/velo-cardio-facial syndrome. EUROPEAN JOURNAL OF HUMAN GENETICS, 7(8), 903-909 [10.1038/sj.ejhg.5200399].
Amati, F; Conti, E; Novelli, A; Bengala, M; Diglio, M; Marino, B; Giannotti, A; Gabrielli, O; Novelli, G; Dallapiccola, B
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/117972
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