Genomic alterations that contribute to the development of isolated and non-isolated congenital diaphragmatic hernia.
J Med Genet
; 48(5): 299-307, 2011 May.
Article
en En
| MEDLINE
| ID: mdl-21525063
ABSTRACT
BACKGROUND:
Congenital diaphragmatic hernia (CDH) is a life threatening birth defect. Most of the genetic factors that contribute to the development of CDH remain unidentified.OBJECTIVE:
To identify genomic alterations that contribute to the development of diaphragmatic defects.METHODS:
A cohort of 45 unrelated patients with CDH or diaphragmatic eventrations was screened for genomic alterations by array comparative genomic hybridisation or single nucleotide polymorphism based copy number analysis.RESULTS:
Genomic alterations that were likely to have contributed to the development of CDH were identified in 8 patients. Inherited deletions of ZFPM2 were identified in 2 patients with isolated diaphragmatic defects and a large de novo 8q deletion overlapping the same gene was found in a patient with non-isolated CDH. A de novo microdeletion of chromosome 1q41q42 and two de novo microdeletions on chromosome 16p11.2 were identified in patients with non-isolated CDH. Duplications of distal 11q and proximal 13q were found in a patient with non-isolated CDH and a de novo single gene deletion of FZD2 was identified in a patient with a partial pentalogy of Cantrell phenotype.CONCLUSIONS:
Haploinsufficiency of ZFPM2 can cause dominantly inherited isolated diaphragmatic defects with incomplete penetrance. These data define a new minimal deleted region for CDH on 1q41q42, provide evidence for the existence of CDH related genes on chromosomes 16p11.2, 11q23-24 and 13q12, and suggest a possible role for FZD2 and Wnt signalling in pentalogy of Cantrell phenotypes. These results demonstrate the clinical utility of screening for genomic alterations in individuals with both isolated and non-isolated diaphragmatic defects.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Genoma Humano
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
J Med Genet
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos