Intellectual disability
Gene: CDK10

CDK10 (cyclin dependent kinase 10)
EnsemblGeneIds (GRCh38): ENSG00000185324
EnsemblGeneIds (GRCh37): ENSG00000185324
OMIM: 603464, Gene2Phenotype
CDK10 is in 3 panels

2 reviews

Louise Daugherty (Genomics England Curator)

Comment on list classification: Changed from Red to Green. Appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene as Green.
Created: 21 Feb 2019, 3:29 p.m.

Comment on publications: Added publication suggested by external reviewer to support gene-disease association, and upgrading of the gene to Green
Created: 21 Feb 2019, 3:25 p.m.

Created: 21 Feb 2019, 3:25 p.m.

Panel version: 2.720

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Biallelic pathogenic variants in CDK10 cause Al Kaissi syndrome (MIM 617694).

Windpassinger et al. (PMID: 28886341) report on 9 individuals from 5 consanguineous families.

The phenotype consisted of developmental delay, intellectual disability (all), growth retardation, spine malformations, and common facial features.

4 pathogenic variants are reported and each was found in the homozygous state in affected individuals [using NM_052988.4 as a reference : c.609-G>A, c.608+1G>A (2 families), c.139delG, as well as an intragenic deletion]. The splice site mutations were shown to behave as LoF (both resulted in frameshift or internal truncation, significantly reduced expression levels and reduced CDK10 activity was demonstrated for 1 variant).

Cdk10-knockout in mice reproduced - at least partly - the human phenotypes. Additional functional studies suggest ciliary defects might contribute to the phenotype.

CDK10 is included in the DD panel of G2P associated with Severe Growth Retardation, Spine Malformations, and Developmental Delays (ID among the assigned phenotypes).

This gene is included in gene panels for ID offered by diagnostic laboratories (incl. Radboudumc).

As a result CDK10 should be considered for upgrade to green.
Created: 20 Dec 2018, 11:09 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Al Kaissi syndrome (MIM 617694)

Publications

28886341

Variants in this GENE are reported as part of current diagnostic practice

Created: 20 Dec 2018, 11:09 a.m.

Panel version: 2.587

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
Victorian Clinical Genetics Services

Phenotypes

Al Kaissi syndrome, 617694
intellectual disability

OMIM

603464

Clinvar variants

Variants in CDK10

Penetrance

None

Publications

28886341

Panels with this gene