Familial Hirschsprung Disease
Gene: L1CAM
Comment when marking as ready: Marked L1CAM as ready: August 3rd 2017.Created: 3 Aug 2017, 9:36 a.m.
Comment on list classification: Updated rating from Amber to Green based on Green expert review and sufficient (>3) cases of L1CAM variants in patients with concurrent X-linked hydrocephalus and Hirschsprung disease.Created: 3 Aug 2017, 9:35 a.m.
Comment on list classification: Updated rating from Red to Amber awaiting external review. >3 cases of L1CAM variants in patients with concurrent X-linked hydrocephalus and Hirschsprung disease.Created: 1 Aug 2017, 2:21 p.m.
Added a 'monogenic-polygenic' tag based on patient in PMID:22344793 who carried both L1CAM and RET variants.Created: 1 Aug 2017, 2:20 p.m.
In 2 brothers with hydrocephalus (MIM:307000) and Hirschsprung disease, Okamoto et al. (2004, PMID:15148591) identified a splice-site mutation in L1CAM.A third case had a nonsense variant in exon 22 (C2974T, Cln992Stop) and hydrocephalus alongside HSCR.Created: 1 Aug 2017, 2:19 p.m.
Jackson et al., 2009 (PMID:19641926) describe a case of a patient with concurrent X-linked hydrocephalus and Hirschsprung disease. The patient was hemizygous for a R558X hemizygous variation in the L1CAM gene.Created: 1 Aug 2017, 2:19 p.m.
Fernández et al., 2012 (PMID:22344793) describe a new patient with concurrent X-linked hydrocephalus and Hirschsprung disease together with a G698R hemizygous mutation in L1CAM. The patient also carried the RET mutation c.73 + 9277T > C.Created: 1 Aug 2017, 2:19 p.m.
Parisi et al. (2002, PMID:11857550) describe a male infant who had severe hydrocephalus (MIM:307000) and Hirschsrpung disease. The patient had a 2254G-A mutation in L1CAM (V752M). Parisi et al. stated that this patient represented the third example of coincident hydrocephalus and Hirschsprung disease in an individual with an identified L1CAM mutation.Created: 1 Aug 2017, 2:19 p.m.
In a child with features of X-linked hydrocephalus (307000) who also had Hirschsprung disease and cleft palate, Okamoto et al. (1997, PMID:9279760) identified a 2-bp deletion of exon 18 in the L1CAM gene, resulting in a frameshift and premature termination. XLH and HSCR may be independent events in this patient, but the authors suggested that L1CAM may contribute to both phenotypes.Created: 1 Aug 2017, 2:18 p.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 Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
This gene has been classified as Amber List (Moderate Evidence).
Publications for L1CAM were set to 28543993; 20860806; 22344793; 11857550; 15148591; 19641926; 9279760
Publications for L1CAM were set to 28543993; 20860806; 22344793; 11857550; 15148591; 19641926
L1CAM was added to Familial Hirschsprung Diseasepanel. Source: Radboud University Medical Center, Nijmegen
Publications for L1CAM were set to 28543993; 20860806; 22344793
Publications for L1CAM were set to 28543993; 20860806
Publications for L1CAM were set to 28543993
L1CAM was created by rfoulger
L1CAM was added to Familial Hirschprungs Diseasepanel. Sources: Alder Hey - Erasmus MC