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Open Access 01-12-2011 | Research article

Comprehensive analysis of RET common and rare variants in a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events

Authors: Rocio Núñez-Torres, Raquel M Fernández, Manuel Jesus Acosta, Maria del Valle Enguix-Riego, Martina Marbá, Juan Carlos de Agustín, Luis Castaño, Guillermo Antiñolo, Salud Borrego

Published in: BMC Medical Genetics | Issue 1/2011

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.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/12/138/prepub

Title: Comprehensive analysis of RET common and rare variants in a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events
Authors: Rocio Núñez-Torres
Raquel M Fernández
Manuel Jesus Acosta
Maria del Valle Enguix-Riego
Martina Marbá
Juan Carlos de Agustín
Luis Castaño
Guillermo Antiñolo
Salud Borrego
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2011
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-12-138

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Comprehensive analysis of RET common and rare variants in a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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