Rare multisystem ciliopathy disorders

Gene: DCDC2

Comment 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

Red List (low evidence)

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

• 27469900
• 27319779
• 25557784

Red List (low evidence)

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

• 25557784
• 27469900

Green List (high evidence)

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

• 27469900, 27319779

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.

I don't know

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 nephronophthisis

Created: 26 Jan 2017, 9:15 a.m.

Only seen in two patients but supported by animal models. Probable DD on G2P

Created: 25 Jan 2017, 12:22 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephronophthisis 19 616217

Publications

• 25557784