Familial Hirschsprung Disease
Gene: SEMA3CComment on list classification: Updated rating from Red to Amber (and added 'watchlist' tag) to match Erwin's review and after discussion with Helen Brittain. On original expert list as cluster of genes (SEMA 3A/C/D), and insufficient cases to currently support causation.Created: 28 Aug 2017, 9:28 a.m.
In a GWAS study PMID:25839327 (Jiang et al., 2015) studied 220 child-parent trios of European ancestry with S-HSCR and identified 9 SNPs at 7 loci, including the semaphorin gene cluster. To assess the role of class 3 semaphorins in HSCR beyond the genetic association, they sequenced SEMA3A,C and D genes in 254 HSCR cases and identified 12 non-synonymous variants. Among these, 3 variants in SEMA3C and 3 variants in SEMA3D were selected as being likely causal based largely on model systems.Created: 14 Aug 2017, 3:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
animal model confirmation. functional test confirming deleterious variantsCreated: 8 May 2017, 10:36 a.m.
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).
Mode of inheritance for SEMA3C was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for SEMA3C were set to 25839327
SEMA3C was added to Familial Hirschprungs Diseasepanel. Sources: Alder Hey - Erasmus MC
SEMA3C was created by rfoulger