Contributions of PHOX2B in the pathogenesis of Hirschsprung disease.

Abstract

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.

• Authors: Raquel María Fernández, Yves Mathieu, Berta Luzón-Toro, Rocío Núñez-Torres, Antonio González-Meneses, Guillermo Antiñolo, Jeanne Amiel, Salud Borrego
• Journal: PloS one (PLoS One) Vol. 8 Issue 1 Pg. e54043 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23342068 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Homeodomain Proteins
• NBPhox protein
• Transcription Factors

Topics

• Case-Control Studies
• Computational Biology
• DNA Mutational Analysis
• Female
• Hirschsprung Disease (genetics, pathology)
• Homeodomain Proteins (genetics)
• Humans
• Male
• Transcription Factors (genetics)