Isolated bladder exstrophy associated with a de novo 0.9 Mb microduplication on chromosome 19p13.12.
Birth Defects Res A Clin Mol Teratol
; 97(3): 133-9, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-23359465
ABSTRACT
BACKGROUND:
The exstrophy-epispadias complex (BEEC) is a urogenital birth defect of varying severity. The causes of the BEEC are likely to be heterogeneous, with individual environmental or genetic risk factors still being largely unknown. In this study, we aimed to identify de novo causative copy number variations (CNVs) that contribute to the BEEC.METHODS:
Array-based molecular karyotyping was performed to screen 110 individuals with BEEC. Promising CNVs were tested for de novo occurrence by investigating parental DNAs. Genes located in regions of rearrangements were prioritized through expression analysis in mice to be sequenced in the complete cohort, to identify high-penetrance mutations involving small sequence changes.RESULTS:
A de novo 0.9 Mb microduplication involving chromosomal region 19p13.12 was identified in a single patient. This region harbors 20 validated RefSeq genes, and in situ hybridization data showed specific expression of the Wiz gene in regions surrounding the cloaca and the rectum between GD 9.5 and 13.5. Sanger sequencing of the complete cohort did not reveal any pathogenic alterations affecting the coding region of WIZ.CONCLUSIONS:
The present study suggests chromosomal region 19p13.12 as possibly involved in the development of CBE, but further studies are needed to prove a causal relation. The spatiotemporal expression patterns determined for the genes encompassed suggest a role for Wiz in the development of the phenotype. Our mutation screening, however, could not confirm that WIZ mutations are a frequent cause of CBE, although rare mutations might be detectable in larger patient samples. 19p13.12, microduplication, bladder exstrophy-epispadias complex, array-based molecular karyotyping, in situ hybridization analysis, copy number variations, WIZ gene.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 19
/
Extrofia Vesical
/
Variações do Número de Cópias de DNA
/
Duplicação Cromossômica
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article