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: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.

journal_name

BMC Med Genet

journal_title

BMC medical genetics

authors

Núñez-Torres R,Fernández RM,Acosta MJ,Enguix-Riego Mdel V,Marbá M,Carlos de Agustín J,Castaño L,Antiñolo G,Borrego S

doi

10.1186/1471-2350-12-138

subject

Has Abstract

pub_date

2011-10-13 00:00:00

pages

138

issn

1471-2350

pii

1471-2350-12-138

journal_volume

12

pub_type

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