De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy.
Maria J Nabais SáHanka VenselaarLaurens WielAurélien TrimouilleEulalie LasseauxSophie NaudionDidier LacombeAmélie PitonCatherine Vincent-DelormeChristiane ZweierAndré ReisRegina TrollmannAnna RuizElisabeth GabauAnnalisa VetroRenzo GuerriniSomayeh BakhtiariMichael C KruerDavid J AmorMonica S CooperEmilia K BijlsmaTahsin Stefan BarakatMarieke F van DoorenMarjon van SlegtenhorstRolph PfundtChristian GilissenMichèl A WillemsenBert B A de VriesArjan P M de BrouwerDavid A KoolenPublished in: Genetics in medicine : official journal of the American College of Medical Genetics (2019)
The wide phenotypic variability associated with likely pathogenic CLTC variants seems to be associated with allelic heterogeneity. The detailed clinical characterization of a larger cohort of individuals with pathogenic CLTC variants is warranted to support the hypothesis that missense and in-frame variants exert a dominant-negative effect, whereas the nonsense and frameshift variants would result in haploinsufficiency.