RT Journal Article
T1 Comprehensive analysis of RET common and rare variant patientsin a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events
A1 Nuñez-Torres, Rocio
A1 Fernandez, Raquel M
A1 Acosta, Manuel Jesus
A1 Enguix-Riego, Maria del Valle
A1 Marba, Martina
A1 de Agustin, Juan Carlos
A1 Castaño, Luis
A1 Antiñolo, Guillermo
A1 Borrego, Salud
K1 Enfermedad de Hirschsprung
K1 Mutación
K1 Proteínas Proto-Oncogénicas c-ret
K1 Polimorfismo de Nucleótido Simple
K1 Análisis Mutacional de ADN
K1 Estudios de Casos y Controles
K1 España
AB 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.
PB BioMed Central
YR 2011
FD 2011-10-13
LK http://hdl.handle.net/10668/292
UL http://hdl.handle.net/10668/292
LA en
NO 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
DS RISalud
RD Apr 17, 2025