Mutations of the RET gene in isolated and syndromic Hirschsprung's disease in human disclose major and modifier alleles at a single locus.

ABSTRACT:

Background

In Hirschsprung's disease (HSCR), a hypomorphic allele of a major gene, RET, accounts for most isolated (non-syndromic) cases, along with other autosomal susceptibility loci under a multiplicative model. However, some syndromic forms of HSCR are monogenic entities, for which the disease causing gene is known.

Objective

To determine whether RET could be considered a modifier gene for the enteric phenotype on the background of a monogenic trait.

Methods

The syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively. The RET locus was genotyped in 143 CCHS patients, among whom 44 had HSCR, and in 30 MWS patients, among whom 20 had HSCR. The distributio

SUBMITTER: de Pontual L 

PROVIDER: S-EPMC2649010 | biostudies-literature | 2006 May

REPOSITORIES: biostudies-literature