Familial Hirschsprung Disease
Gene: GFRA1Added 'watchlist' tag to be notified of additional cases.Created: 18 Oct 2017, 9:05 a.m.
Added 'watchlist' tag to be notified of additional cases.Created: 18 Oct 2017, 9:05 a.m.
Comment on list classification: Updated rating from Red to Amber. Although GFRA1 has a Green expert rating, there is limited literature evidence to support a causation role in Hirschsprung. Further definitive cases are required to form a diagnostic rating.Created: 18 Oct 2017, 8:40 a.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. Variants were found in RET and GDNF but not in GFRA1.Created: 14 Aug 2017, 12:16 p.m.
Mouse model summarised in PMID:27370713: Total intestinal aganglionosis in homozygotes. Heterozygotes have decreased neuron size but normal numbers. PMID:17507417 also presents mouse model.Created: 1 Aug 2017, 3:30 p.m.
PMID:9545641 (Angrist et al., 1998) failed to detect linkage of GFRA1 in HSCR patients, and no sequence variants were found to be in significant excess in patients.Created: 1 Aug 2017, 3:25 p.m.
PMID:12624147 (Borrego et al., 2003) found a large germline deletion in the 5' UTR of GFRA1 of unknown significance in an HSCR case. Analysis of the unaffected father and three unaffected sibs showed this identical deletion.Created: 1 Aug 2017, 3:22 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Variants in this GENE are reported as part of current diagnostic practice
animal model confirmation. functional test confirming deleterious variants. digenicCreated: 8 May 2017, 10:36 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 GFRA1 were set to 28543993; 27370713; 9545641; 17507417; 12624147
Publications for GFRA1 were set to 28543993; 27370713; 9545641
Publications for GFRA1 were set to 28543993; 27370713
Publications for GFRA1 were set to 28543993
GFRA1 was added to Familial Hirschprungs Diseasepanel. Sources: Alder Hey - Erasmus MC
GFRA1 was created by rfoulger