Limb disorders

Gene: CCND2

Comment on mode of pathogenicity: PMID: 24705253 functional analysis suggests gain of function

Created: 9 Dec 2018, 11:36 p.m.

Comment when marking as ready: Rated green based on sufficient evidence.

Created: 17 Oct 2018, 4:35 p.m.

Comment on list classification: More than 3 unrelated cases/families with plausible disease causing variants in this gene.

Created: 17 Oct 2018, 3:31 p.m.

In OMIM and Gene2Phenotype CCND2 is associated with Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3.

Mirzaa et al. (2014)(PMID: 24705253) identified heterozygous mutations in the CCND2 gene in 12 probands with megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-3. 7 different mutations were identified. All probands except 1 showed polydactyly of either the hands or feet or both. The mutations occurred de novo in all patients from whom parental DNA was available, except for 1 parent who was mosaic for the mutation. All of the mutations either altered conserved residues, or truncated the protein before a phosphorylation site necessary for subsequent protein degradation. Transfection of the CCND2 mutations into HEK293 cells resulted in abnormal accumulation of unphosphorylated, degradation-resistant cyclin D2.

Created: 17 Oct 2018, 3:26 p.m.