Epileptic encephalopathy

Gene: CLTC

Green List (high evidence)

Comment on list classification: Added new Green gene to Epileptic encephalopathy panel, there is enough evidence to support the epilepsy phenotype.

Created: 26 Feb 2018, 5:25 p.m.

Added from the Intellectual Disability review. There are 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. 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: 26 Feb 2018, 5:24 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Mental retardation, autosomal dominant 56, 617854; Autosomal dominant non-syndromic intellectual disability; Epilepsy and intellectual disability

Publications

• 26822784
• 29100083