Molecular Characteristics

CCDC186 associated developmental and epileptic encephalopathy (DEE) is inherited in an autosomal recessive fashion with to data only biallelic loss-of-function variants being described. Thus the molecular mechanism seems to be a complete lack of protein. It is expected that also missense variants will be classified as pathogenic in the future. There is currently no evidence for other modes of inheritance, for incomplete penetrance or hypomorphic alleles. Diagnostic testing should be whole exome sequencing (WES) or preferably whole genome sequencing (WGS) as no testing for exonic deletions of duplications by MLPA is currently commercially available.