Rare multisystem ciliopathy disorders
Gene: DCDC2Comment on list classification: Downgraded rating from Amber to Red following advice from Genomics England clinical team: Not a multi-system ciliopathy and therefore Red rating is appropriate. Note that DCDC2 is Green on the
Neonatal cholestasis panel, which is the appropriate panel for this gene.Created: 27 Jun 2019, 8:17 a.m. | Last Modified: 27 Jun 2019, 8:17 a.m.
Panel Version: 1.115
Gene should be red for Rare multisystem ciliopathy disorders.
Evidence that gene variants are responsible for neonatal sclerosing cholangitis; however, this phenotype is not currently included in the criteria for rare multisystem ciliopathy disorders.Created: 17 Sep 2018, 10:58 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Based on published evidence this gene should be RED for the Rare multisystem ciliopathy disorders.
This is because there is only ONE patient (in 25557784) who has a renal phenotype plus hepatic disease. The paper has lots of functional data. This is the second paper I have seen from this team where the functional data is strong but the clinical phenotyping is exceptionally weak.
The other patient in this report (25557784) has hepatic fibrosis only and does not have renal disease. In the second paper (27469900) the patients with mutations have neonatal sclerosing cholangitis.
There is evidence that this gene affects cilial function, but the phenotype most consistently reported does not fall within the current clinical phenotype criteria for rare multisystem ciliopathy disorders.
There are two options: either widen the phenotype criteria for rare multi-system ciliopathies to include hepatic fibrosis, or just keep this gene within cholestasis section.Created: 5 Sep 2018, 10:32 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
hepatic fibrosis; end-stage renal disease; primary sclerosing cholangitis
Publications
Although neonatal sclerosing cholangitis is not classically considered a ciliopathy, the published literature specifically provides evidence for abnormal cilia in patients with bi-allelic variants in this gene.Created: 3 Aug 2018, 7:03 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: I am unsure whether Neonatal sclerosing cholangitis should be included on this panel - if so, there is enough evidence for this gene to be green - see publications PMID:27469900 and PMID: 27319779.Created: 25 Jan 2017, 4:48 p.m.
Comment on list classification: Most often associated with neonatal sclerosing cholangitis which is not relevant phenotype for this panel. Await further evidence of association with nephronophthisisCreated: 26 Jan 2017, 9:15 a.m.
Only seen in two patients but supported by animal models. Probable DD on G2PCreated: 25 Jan 2017, 12:22 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Nephronophthisis 19 616217
Publications
Gene: dcdc2 has been classified as Red List (Low Evidence).
Promoted to version 1 by Alice Gardham on 26th January 2017
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Amber List (Moderate Evidence).
Mode of inheritance for DCDC2 was changed to BIALLELIC, autosomal or pseudoautosomal
Publications for DCDC2 were set to 27319779 - biallelic missense variants reported in four affected children with Neonatal sclerosing cholangitis; 27469900 - 7 out of 24 patients with 7 with biallelic protein-truncating variants in DCDC2 (6 of 19 families); 25557784 - in vitro/in vivo evidence; 22558177 - expression data for the transcriptome of ciliated cells
Publications for DCDC2 were set to 27319779 - biallelic missense variants reported in four affected children with Neonatal sclerosing cholangitis; 27469900 - 7 out of 24 patients with 7 with biallelic protein-truncating variants in DCDC2 (6 of 19 families); 25557784 - in vitro/in vivo evidence; 22558177 - expression data for the transcriptome of ciliated cells
Publications for DCDC2 were set to 27319779 - Neonatal sclerosing cholangitis cases; 27469900 - Neonatal sclerosing cholangitis cases; 25557784 - in vitro/in vivo evidence; 22558177 - expression data for the transcriptome of ciliated cells
Phenotypes for DCDC2 were set to Nephronophthisis 19, 616217; Neonatal sclerosing cholangitis
DCDC2 was added to Rare multisystem ciliopathy disorderspanel. Source: Orphanet
DCDC2 was added to Rare multisystem ciliopathy disorderspanel. Sources: Radboud University Medical Center, Nijmegen
Phenotypes for gene DCDC2 were set to Nephronophthisis 19, 616217;?Deafness, autosomal recessive 66, 610212
DCDC2 was created by ellenmcdonagh
DCDC2 was added to Rare multisystem ciliopathy disorderspanel. Sources: Expert list