ABSTRACT
La enfermedad de Hirschsprung (HSCR) es un desorden congénito caracterizado por la ausencia de células ganglionares a lo largo del tracto gastrointestinal. Está causada por defectos en la migración de las células del sistema nervioso entérico durante el desarrollo embrionario. La mejora de tratamientos quirúrgicos ha disminuido la mortalidad de los pacientes, lo que facilita el estudio genético de enfermos y sus familiares. Aunque se desconoce la causa genética de la enfermedad, se sospecha que el oncogén RET es el principal involucrado. Se han encontrado alteraciones en este gen en enfermos con HSCR, por lo que algunos autores sugieren que ciertos polimorfismos (SNPs) en el gen podrían causar cierta predisposición genética a padecer esta enfermedad. Nuestro trabajo ha consistido en el análisis del gen RET en pacientes con diagnóstico de HSCR mediante secuenciación directa y genotipado con sondas Taqman®.Los resultados obtenidos indican que ciertos alelos de los polimorfismos p.Leu769Leu (c.2307T>G, Exón 13) p.Gly691Ser (c.2071G>A, Exón 11) y p.Ser904Ser (c.2712C>G, Exón 15) están asociados a losenfermos HSCR, ya que existen diferencias significativas respecto ala población sana (AU)
Hirschsprungs disease (HSCR) is a developmental disorder characterized by the absence of the enteric ganglia along the intestine. Is regarded as the consequence of the premature arrest of the migration of neural crest cells in the hindgut during the embryonic development to form the enteric nervous system (ENS). Is considered, therefore, a neurocristopathy. The development of surgical approaches has importantly decreased mortality and morbility of Hirschsprungs patients, which has allowed the emergence of genetic studies of patients and their families. Although the genetic cause of the disease is still unknown, the RET oncogene is the main involved. Alterations in this gene have been found in HSCR patients, so many authors suggest that certain polymorphisms(SNPs) in this gene could be responsible of genetic predisposition to have the disease. Our work has consisted in the genetic analysis of the RET gene in HSCR patients using direct sequencing and genotyping with Taq-Man® probes. Our results show that some alleles of the polymorphismsp.Leu769Leu (c.2307T>G, Exon 13) p.Gly691Ser (c.2071G>A, Exon11) and p.Ser904Ser (c.2712C>G, Exon 15) are associated to the disease since there are significant differences from the healthy population (AU)
Subject(s)
Humans , Male , Female , Infant , Polymorphism, Genetic , Hirschsprung Disease/genetics , Proto-Oncogene Proteins c-ret/genetics , Base Sequence/genetics , Exons/genetics , Genotyping TechniquesABSTRACT
Hirschsprung's disease (HSCR) is a developmental disorder characterised by the absence of the enteric ganglia along the intestine. Is regarded as the consequence of the premature arrest of the migration of neural crest cells in the hindgut during the embryonic development to form the enteric nervous system (ENS). Is considered, therefore, a neurocristopathy. The development of surgical approaches has importantly decreased mortality and morbility of Hirschsprung's patients, which has allowed the emergence of genetic studies of patients and their families. Although the genetic cause of the disease is still unknown, the RET oncogene is the main involved. Alterations in this gene have been found in HSCR patients, so many authors suggest that certain polymorphisms (SNPs) in this gene could be responsible of genetic predisposition to have the disease. Our work has consisted in the genetic analysis of the RET gene in HSCR patients using direct sequencing and genotyping with TaqMan probes. Our results show that some alleles of the polymorphisms p.Leu769Leu (c.2307T>G, Exon 13) p.Gly691Ser (c.2071G>A, Exon 11) and p.Ser904Ser (c.2712C>G, Exon 15) are associated to the disease since there are significant differences from the healthy population.
