Fernández, Raquel MaríaSánchez-Mejías, AvenciaRuiz-Ferrer, Maria MacarenaLópez-Alonso, ManuelAntiñolo, GuillermoBorrego, Salud2015-11-232015-11-232009-03Fernández RM, Sánchez-Mejías A, Ruiz-Ferrer MM, López-Alonso M, Antiñolo G, Borrego S. Is the RET proto-oncogene involved in the pathogenesis of intestinal neuronal dysplasia type B? Mol Med Rep 2009; 2(2):265-70http://hdl.handle.net/10668/2066Journal Article;Hirschsprung disease (HSCR) is defined by the absence of intramural ganglia of Meissner and Auerbach along variable lengths of the gastrointestinal tract. Intestinal neuronal dysplasia (IND) type B is characterized by the malformation of the parasympathetic submucous plexus of the gut. A connection appears to exist between these two enteric nervous system abnormalities. Due to the major role played by the RET proto-oncogene in HSCR, we sought to determine whether this gene was also related to INDB. dHPLC techniques were employed to screen the RET coding region in 23 patients presenting with INDB and 30 patients with a combined HSCR+INDB phenotype. In addition, eight RET single nucleotide polymorphisms (SNPs) were strategically selected and genotyped by TaqMan technology. The distribution of SNPs and haplotypes was compared among the different groups of patients (INDB, HSCR+INDB, HSCR) and the controls. We found several RET mutations in our patients and some differences in the distribution of the RET SNPs among the groups of study. Our results suggest an involvement of RET in the pathogenesis of intestinal INDB, although by different molecular mechanisms than those leading to HSCR. Further investigation is warranted to elucidate these precise mechanisms and to clarify the genetic nature of INDB.enEnteric nervous system disordersHirschsprung diseaseIntestinal neuronal dysplasia type BRET proto-oncogeneSusceptibility haplotypesSistema Nervioso EntéricoGangliosGenotipoHaplotiposEnfermedad de HirschsprungHumanosMutaciónMalformaciones del sistema serviosoFenotipoPlexo submucosoProto-oncogenesPolimorfismo de nucleótido simpleMedical Subject Headings::Anatomy::Nervous System::Peripheral Nervous System::Autonomic Nervous System::Enteric Nervous SystemMedical Subject Headings::Anatomy::Nervous System::GangliaMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::GenotypeMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::HaplotypesMedical Subject Headings::Diseases::Digestive System Diseases::Digestive System Abnormalities::Hirschsprung DiseaseMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::MutationMedical Subject Headings::Anatomy::Nervous System::Peripheral Nervous System::Autonomic Nervous System::Autonomic Pathways::Myenteric PlexusMedical Subject Headings::Diseases::Nervous System Diseases::Nervous System MalformationsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::PhenotypeMedical Subject Headings::Anatomy::Nervous System::Peripheral Nervous System::Autonomic Nervous System::Autonomic Pathways::Submucous PlexusMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Neoplasm::Oncogenes::Proto-OncogenesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotideresearch article21475823open access10.3892/mmr_000000941791-2997PMC2362115