RET somatic mutations are underrecognized in Hirschsprung disease

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Mutations in SCG10 Are Not Involved in Hirschsprung Disease

Hirschsprung disease (HSCR) is a congenital malformation characterized by the absence of enteric neurons in the distal part of the colon. Several genes have been implicated in the development of this disease that together account for 20% of all cases, implying that other genes are involved. Since HSCR is frequently associated with other congenital malformations, the functional characterization ...

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c-Ret-mediated hearing loss in mice with Hirschsprung disease.

A significantly increased risk for dominant sensorineural deafness in patients who have Hirschsprung disease (HSCR) caused by endothelin receptor type B and SOX10 has been reported. Despite the fact that c-RET is the most frequent causal gene of HSCR, it has not been determined whether impairments of c-Ret and c-RET cause congenital deafness in mice and humans. Here, we show that impaired phosp...

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Differential contributions of rare and common, coding and noncoding Ret mutations to multifactorial Hirschsprung disease liability.

The major gene for Hirschsprung disease (HSCR) encodes the receptor tyrosine kinase RET. In a study of 690 European- and 192 Chinese-descent probands and their parents or controls, we demonstrate the ubiquity of a >4-fold susceptibility from a C-->T allele (rs2435357: p = 3.9 x 10(-43) in European ancestry; p = 1.1 x 10(-21) in Chinese samples) that probably arose once within the intronic RET e...

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1 TITLE : TTF - 1 and RET promoter SNPs : regulation of RET transcription in Hirschsprung ' s disease

Single nucleotide polymorphisms (SNPs) of the coding regions of RET are associated with Hirschsprung’s disease (HSCR, aganglionic megacolon,). These SNPs, individually or combined, may act as a low penetrance susceptibility locus or/and be in linkage disequilibrium (LD) with another susceptibility locus located in RET regulatory regions. Because two RET promoter SNPs have been found associated ...

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Functional haplotypes of the RET proto-oncogene promoter are associated with Hirschsprung disease (HSCR).

The activation of the RET signaling pathway during embryogenesis is a crucial prerequisite for a directional migration of enteric nervous system progenitor cells. Loss-of-function germline mutations of the RET proto-oncogene are reported in familial and sporadic cases of Hirschsprung disease (HSCR) with a variable frequency. Furthermore, variants of several RET polymorphisms are over- or under-...

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ژورنال

عنوان ژورنال: Genetics in Medicine

سال: 2017

ISSN: 1098-3600,1530-0366

DOI: 10.1038/gim.2017.178