Familial Hirschsprung Disease
Gene: NRTNComment when marking as ready: Marked as ready: 14th August 2017.Created: 14 Aug 2017, 2:41 p.m.
Comment on list classification: Kept rating as Red: Although NRTN is on the original submitted list, publications report co-occurence of Neurturin and RET variants in HSCR patients. Plus red expert review.Created: 14 Aug 2017, 2:41 p.m.
PMID:21206993 (Ruiz-Ferrer et al., 2011) report association of NRTN gene with HSCR. Mutational screening of GDNF, NRTN, ARTN and PSPN was performed on 217 patients with HSCR (199 sporadic cases and 27 familial cases belonging to 13 different families). The authors identify a F127L variant in NRTN in a sporadic Hirschsprung patient: functional analysis shows that F127L results in reduced phosphorylation of RET. All patients were found to be homozygous or heterozygous for the common RET variant within the transcriptional enhancer in intron 1 of RET.Created: 3 Aug 2017, 2:33 p.m.
Added polygenic tag based on co-occurring RET and NRTN mutations in patients in PMID:9700200.Created: 3 Aug 2017, 10:55 a.m.
Neurturin is a ligand for the receptor RET. PMID:9700200 (Doray et al 1998) report a heterozygous missense NRTN mutation in a large non-consanguineous family including 4 children affected with a severe aganglionosis phenotype extending up to the small intestine. It appears that the NRTN mutation reported here is not sufficient to cause HSCR, and this multiplex family also segregates a RET mutation.Created: 3 Aug 2017, 10:40 a.m.
Publications
18th October 2017: Revised and approved to Version 1.0 after expert and curator review. An expert list from Mr. Simon Kenny and Professor Robert Hofstra's groups (Alder Hey - Erasmus MC) formed the basis of the original panel. The expert list was then expanded based on a review of literature. Many of the literature genes remain red on the V1.0 panel as they were identified through association studies and/or they represent susceptibility/risk factors for Hirschsprung's disease (HSCR). Sumita Chhabra (Alder Hey) and Erwin Brosens (Erasmus) provided extensive feedback for genes on the panel, together with reviews from Merce Garcia-Barcelo.
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
Publications for NRTN were set to 28543993; 9700200; 21206993
Publications for NRTN were set to 28543993; 9700200
Publications for NRTN were set to 28543993
NRTN was created by rfoulger
NRTN was added to Familial Hirschprungs Diseasepanel. Sources: Alder Hey - Erasmus MC