Fernández, Raquel MaríaMathieu, YvesLuzón-Toro, BertaNúñez Torres, RocíoGonzález-Meneses, AntonioAntiñolo, GuillermoAmiel, JeanneBorrego, Salud2025-01-122025-01-122013Fernández, R.M., Mathieu, Y., Luzón-Toro, B., et al. (2013). Contributions of PHOX2B in the pathogenesis of Hirschsprung disease. PLoS One, 8(1):e54043.1932-6203https://hdl.handle.net/10641/5564Hirschsprung 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articleopen access10.1371/journal.pone.0054043