Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/292
Título : Comprehensive analysis of RET common and rare variant patientsin a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events
Autor : Nuñez-Torres, Rocio
Fernandez, Raquel M
Acosta, Manuel Jesus
Enguix-Riego, Maria del Valle
Marba, Martina
de Agustin, Juan Carlos
Castaño, Luis
Antiñolo, Guillermo
Borrego, Salud
Filiación: [Nuñez-Torres R; Fernandez RM; Acosta MJ; Enguix-Riego MV, Antiñolo G; Borrego S] Unidad de Gestión Clínica de Genética,Reproducción y Medicina Fetal. Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Sevilla, Spain.[Marbá M] Departamento de Genómica y Bioinformática. Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain. [de Agustin,JC] Unidad de Gestión Clínica de Cirugía Infantil, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Castaño L] Grupo de investigación en Endocrinología y Diabetes, Hospital de Cruces, Vizcaya, Spain.
Palabras clave : Enfermedad de Hirschsprung
Mutación
Proteínas Proto-Oncogénicas c-ret
Polimorfismo de Nucleótido Simple
Análisis Mutacional de ADN
Estudios de Casos y Controles
España
MeSH: Medical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Digestive System Abnormalities::Hirschsprung Disease
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Oncogene Proteins::Proto-Oncogene Proteins c-ret
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::DNA Mutational Analysis
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Case-Control Studies
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Geographicals::Geographic Locations::Europe::Spain
Fecha de publicación : 13-Oct-2011
Editorial : BioMed Central
Cita Bibliográfica: Nuñez-Torres R, Fernandez RM, Acosta MJ, Enguix-Riego MV, Marba M, de Agustin JC, et al. Comprehensive analysis of RET common and rare variants in a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events. BMC Med Genet 2011;12:138
Abstract: Background. RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology. In the present study, we have performed a comprehensive study of our HSCR series evaluating the involvement of both RET rare variants (RVs) and common variants (CVs) in the context of the disease. Methods. RET mutational screening was performed by dHPLC and direct sequencing for the identification of RVs. In addition Taqman technology was applied for the genotyping of 3 RET CVs previously associated to HSCR, including a variant lying in an enhancer domain within RET intron 1 (rs2435357). Statistical analyses were performed using the SPSS v.17.0 to analyze the distribution of the variants. Results. Our results confirm the strongest association to HSCR for the "enhancer" variant, and demonstrate a significantly higher impact of it in male versus female patients. Integration of the RET RVs and CVs analysis showed that in 91.66% of cases with both kinds of mutational events, the enhancer allele is in trans with the allele bearing the RET RV. Conclusions. A gender effect exists on both the transmission and distribution of rare coding and common HSCR causing mutations. In addition, these RET CVs and RVs seem to act in a synergistic way leading to HSCR phenotype.
URI: http://hdl.handle.net/10668/292
Versión del editor : http://www.biomedcentral.com/1471-2350/12/138
DOI: 10.1186/1471-2350-12-138
ISSN : 1471-2350 (online)
Appears in Collections:01- Artículos - IBIS. Instituto de Biomedicina de Sevilla
01- Artículos - Hospital Virgen del Rocío

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