Contributions of PHOX2B in the pathogenesis of Hirschsprung disease.
Hirschsprung disease (HSCR) is a congenital malformation of the hindgut resulting from a disruption of neural crest cell migration during embryonic development. It has a complex genetic aetiology with several genes involved in its pathogenesis. PHOX2B plays a key function in the development of neura...
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doaj-57fa4cbc69e3434b89f68c1eb04658d82020-11-25T01:13:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5404310.1371/journal.pone.0054043Contributions of PHOX2B in the pathogenesis of Hirschsprung disease.Raquel María FernándezYves MathieuBerta Luzón-ToroRocío Núñez-TorresAntonio González-MenesesGuillermo AntiñoloJeanne AmielSalud BorregoHirschsprung disease (HSCR) is a congenital malformation of the hindgut resulting from a disruption of neural crest cell migration during embryonic development. It has a complex genetic aetiology with several genes involved in its pathogenesis. PHOX2B plays a key function in the development of neural crest derivatives, and heterozygous mutations cause a complex dysautonomia associating HSCR, Congenital Central Hypoventilation Syndrome (CCHS) and neuroblastoma (NB) in various combinations. In order to determine the role of PHOX2B in isolated HSCR, we performed a mutational screening in a cohort of 207 Spanish HSCR patients. Our most relevant finding has been the identification of a de novo and novel deletion (c.393_410del18) in a patient with HSCR. Results of in silico and functional assays support its pathogenic effect related to HSCR. Therefore our results support that PHOX2B loss-of-function is a rare cause of HSCR phenotype.http://europepmc.org/articles/PMC3544660?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Raquel María Fernández Yves Mathieu Berta Luzón-Toro Rocío Núñez-Torres Antonio González-Meneses Guillermo Antiñolo Jeanne Amiel Salud Borrego |
spellingShingle |
Raquel María Fernández Yves Mathieu Berta Luzón-Toro Rocío Núñez-Torres Antonio González-Meneses Guillermo Antiñolo Jeanne Amiel Salud Borrego Contributions of PHOX2B in the pathogenesis of Hirschsprung disease. PLoS ONE |
author_facet |
Raquel María Fernández Yves Mathieu Berta Luzón-Toro Rocío Núñez-Torres Antonio González-Meneses Guillermo Antiñolo Jeanne Amiel Salud Borrego |
author_sort |
Raquel María Fernández |
title |
Contributions of PHOX2B in the pathogenesis of Hirschsprung disease. |
title_short |
Contributions of PHOX2B in the pathogenesis of Hirschsprung disease. |
title_full |
Contributions of PHOX2B in the pathogenesis of Hirschsprung disease. |
title_fullStr |
Contributions of PHOX2B in the pathogenesis of Hirschsprung disease. |
title_full_unstemmed |
Contributions of PHOX2B in the pathogenesis of Hirschsprung disease. |
title_sort |
contributions of phox2b in the pathogenesis of hirschsprung disease. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Hirschsprung disease (HSCR) is a congenital malformation of the hindgut resulting from a disruption of neural crest cell migration during embryonic development. It has a complex genetic aetiology with several genes involved in its pathogenesis. PHOX2B plays a key function in the development of neural crest derivatives, and heterozygous mutations cause a complex dysautonomia associating HSCR, Congenital Central Hypoventilation Syndrome (CCHS) and neuroblastoma (NB) in various combinations. In order to determine the role of PHOX2B in isolated HSCR, we performed a mutational screening in a cohort of 207 Spanish HSCR patients. Our most relevant finding has been the identification of a de novo and novel deletion (c.393_410del18) in a patient with HSCR. Results of in silico and functional assays support its pathogenic effect related to HSCR. Therefore our results support that PHOX2B loss-of-function is a rare cause of HSCR phenotype. |
url |
http://europepmc.org/articles/PMC3544660?pdf=render |
work_keys_str_mv |
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