De novo frameshift mutation in COUP-TFII (NR2F2) in human congenital diaphragmatic hernia.
Am J Med Genet A
; 170(9): 2457-61, 2016 09.
Article
en En
| MEDLINE
| ID: mdl-27363585
ABSTRACT
COUP-TFII (NR2F2) is mapped to the 15q26 deletion hotspot associated with the common and highly morbid congenital diaphragmatic hernia (CDH). Conditional homozygous deletions of COUP-TFII in mice result in diaphragmatic defects analogous to the human Bochdalek-type hernia phenotype. Despite evidence from animal models however, mutations in the coding sequence of COUP-TFII have not been reported in patients, prompting the speculation that additional coding or non-coding sequences in the 15q26 locus are necessary for diaphragmatic hernias to develop. In this report, we describe a case of a patient with a heterozygous de novo COUP-TFII frameshift mutation, presenting with CDH and an atrial septal defect. The p.Pro33AlafsTer77 mutation specifically disrupts protein isoform 1 which contains the DNA binding domain. In addition, we review other COUP-TFII sequence variations and deletions that have been described in cases of CDH. We conclude that COUP-TFII mutations can cause diaphragmatic hernias, and should be included in the differential diagnosis of CDH patients, particularly those with comorbid congenital heart defects. © 2016 Wiley Periodicals, Inc.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
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Mutación del Sistema de Lectura
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Factor de Transcripción COUP II
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Estudios de Asociación Genética
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Hernias Diafragmáticas Congénitas
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Female
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Humans
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Male
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Newborn
Idioma:
En
Año:
2016
Tipo del documento:
Article