Familial Hirschsprung Disease
Gene: GDNFComment when marking as ready: Marked as ready (Amber): 29th August 2017. Kept rating as Amber after clinical input from Helen Brittain: although GDNF has 1 expert green review, Erwin Brosens notes a digenic inheritance. Further correspondence with Sumita Chhabra confirmed that it is rare to have a single variant in GDNF.Created: 29 Aug 2017, 3:18 p.m.
PMID:19282698 determined the prevalence of CAKUT (congenital anomalies of the kidney and urinary tract) in HSCR patients. 84 HSCR patients consecutively admitted to their department between July 2006 and July 2007 underwent analysis. 21 patients with HSCR had associated CAKUT. GDNF mutations were found in 2 HSCR patients (plus 1 CAKUT patient).Created: 14 Aug 2017, 12:19 p.m.
Ivanchuk et al. 1996 (PMID:8968758) identified a mutation in GDNF (T154S) in a sporadic HSCR patient (no RET mutation was found). They suggest GDNF variants may be causative in some HSCR cases.Created: 3 Aug 2017, 9:29 a.m.
Salomon et al. (1996, PMID:8896569) analyzed GDNF mutations in 173 Hirschsprung disease patients and concluded that mutations in GDNF per se are neither necessary nor sufficient to cause HSCR, but may influence susceptibility to the disease especially in conjunction with other loci such as RET.
Created: 3 Aug 2017, 9:29 a.m.
Polygenic interaction between RET and GDNF suggested by Angrist et al., 1996 (PMID:8896568) based on a patient with a known RET mutation plus a GDNF variant (R93W).Created: 3 Aug 2017, 9:29 a.m.
Mouse model summarised in PMID:27370713: Total intestinal aganglionosis in homozygotes; hypoganglionosis throughout intestine of heterozygotes.Created: 1 Jun 2017, 3:35 p.m.
digenic inheritance; complex inheritanceCreated: 3 Aug 2017, 6:17 a.m.
Mode of inheritance
Other
Variants in this GENE are reported as part of current diagnostic practice
animal model confirmation. functional test confirming deleterious variants. DigenicCreated: 16 Aug 2017, 6:54 a.m.
Variants in this GENE are reported as part of current diagnostic practice
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 Amber List (Moderate Evidence).
Publications for GDNF were set to 28543993; 27370713; 8896568; 8896569; 8968758
Phenotypes for GDNF were set to susceptibility to Hirschsprung disease 3, 613711; {Hirschsprung disease, susceptibility to, 3}, 613711; Hirschsprung Disease, Dominant; short-segment HSCR; long-segment HSCR
GDNF was added to Familial Hirschsprung Diseasepanel. Source: Illumina TruGenome Clinical Sequencing Services Model of inheritance for gene GDNF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
GDNF was added to Familial Hirschsprung Diseasepanel. Source: Radboud University Medical Center, Nijmegen
Publications for GDNF were set to 28543993; 27370713
Publications for GDNF were set to 28543993
GDNF was created by rfoulger
GDNF was added to Familial Hirschprungs Diseasepanel. Sources: Alder Hey - Erasmus MC