Intellectual disability update Jan 2018

Gene: CLTC

Comment when marking as ready: Sufficient cases, appropriate phenotype

Created: 5 Mar 2018, 11:33 a.m.

Comment on list classification: Changed gene from status Amber to Green after internal review with clinical team. It was noted that it was helpful to see that the variants include truncations and are from several sources.

Created: 26 Feb 2018, 5:18 p.m.

This is a probable DD gene in Gene2Phenotype for Epilepsy and intellectual disability and a possible DD gene in Gene2Phenotype for Overgrowth intellectual disability

Created: 20 Feb 2018, 1:41 p.m.

Comment on list classification: Changed rating from Red to Amber. To be discussed with internal clinical team regarding whether this gene could be rated Green on the ID panel.

Created: 20 Feb 2018, 1:26 p.m.

Comment on publications: added publications to support the ID phenotype. More than three unrelated cases with autosomal dominant mental retardation-56 (MRD56). De Mari et al., 2016 (PMID:26822784) identified a de novo heterozygous frameshift mutation in the CLTC gene in a young patient, the authors postulated haploinsufficiency of CLTC as the pathogenetic mechanism. Hamdan et al., 2017 (PMID:29100083) identified de novo heterozygous missense mutations in the CLTC gene in 12 unrelated patients with MRD56 in several cohorts of patients with developmental delay and epilepsy. There were 5 truncating mutations, 2 small in-frame deletions, 1 splice site mutation, and 3 missense mutations, 1 of which was recurrent and found in 3 unrelated patients. Individuals with refractory epilepsy were found to carry variants in the first section of the clathrin light chain-binding domain, whereas truncating mutations affecting the C terminus tended to be associated with hypotonia, global developmental delay, and intellectual disability.
In both studies by De Mari et al. and Hamdan et al. functional studies of the variant and studies of patient cells were not performed.

Created: 20 Feb 2018, 1:13 p.m.

Comment on phenotypes: added phenotype from OMIM, orphanet and DDD project

Created: 20 Feb 2018, 12:58 p.m.