Skeletal dysplasia

Gene: PKDCC

Green List (high evidence)

We reported 8 cases from 7 independent families with phenotype in keeping with 2 families published by Sajan et al.

Created: 10 Mar 2023, 10:57 a.m. | Last Modified: 10 Mar 2023, 10:57 a.m.

Panel Version: 3.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
rhizomelia

Publications

• https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.14324

Based on the expert review by Michael Oldridge (NHS), the mouse model in PMID: 30478137 is of compatible phenotype with the disease. Therefore, there is enough evidence for this gene to be Green. This gene has been tagged for-review at the next panel review.

Created: 1 Feb 2021, 11:40 a.m. | Last Modified: 1 Feb 2021, 11:40 a.m.

Panel Version: 2.81

Green List (high evidence)

2 unrelated individuals with homozygous pathogenic variants (+1 splice site and nonsense). Both with rhizomelic shortening and other dysmorphic features. K/O mouse model has compatible phenotype with long bone shortening and craniofacial abnormalities.

Created: 30 Jan 2021, 4:36 p.m. | Last Modified: 30 Jan 2021, 4:36 p.m.

Panel Version: 2.80

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
rhizomelic limb shortening; facial dysmorphism

Publications

• 30478137

I don't know

Comment on list classification: Further expert review from Alistair Pagnamenta supports the green rating of this gene. No change in rating needed as is green already.

Created: 9 May 2023, 4:23 p.m. | Last Modified: 9 May 2023, 4:23 p.m.

Panel Version: 4.2

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 6 Mar 2022, 5:41 p.m. | Last Modified: 6 Mar 2022, 5:41 p.m.

Panel Version: 2.176

Comment on list classification: Promoting this gene from grey to amber. 2 cases plus mouse knockout, with a similar but not exactly the same phenotype to the cases reported.

Created: 20 Jan 2021, 12:34 p.m. | Last Modified: 20 Jan 2021, 12:34 p.m.

Panel Version: 2.53

Associated with Rhizomelic limb shortening with dysmorphic features #618821 (AR) in OMIM.

As reported by Expert Reviewer PMID:30478137 (Sajan et al 2019) reports two cases of patients with rhizomelic shortening of limbs and dysmorphic features who were found by exome sequencing to have homozgyous variants in PKDCC (one a nonsense variant, one a splice variant). Parents were heterozygous for the variants. PMID:19097194 (Imuta et al 2009) reports that Pkdcc-/- mice have abnormalities at birth that include short limbs, cleft palate, sternal dysraphia, and shortened intestine.

Created: 20 Jan 2021, 12:32 p.m. | Last Modified: 20 Jan 2021, 12:32 p.m.

Panel Version: 2.52

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Rhizomelic limb shortening with dysmorphic features OMIM:618821; rhizomelic limb shortening with dysmorphic features MONDO:0032935

Publications

• 30478137
• 19097194

I don't know

Two unrelated consanguineous families reported with different homozygous variants
Pre-existing mouse model has similar phenotype
Sources: Literature

Created: 23 Apr 2020, 3:37 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Rhizomelia; dysmorphism

Publications

• 30478137
• 19097194