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dc.contributor.authorSa, MJN
dc.contributor.authorVenselaar, H
dc.contributor.authorWiel, L
dc.contributor.authorTrimouille, A
dc.contributor.authorLasseaux, E
dc.contributor.authorNaudion, S
dc.contributor.authorLacombe, D
dc.contributor.authorPiton, A
dc.contributor.authorVincent-Delorme, C
dc.contributor.authorZweier, C
dc.contributor.authorReis, A
dc.contributor.authorTrollmann, R
dc.contributor.authorRuiz, A
dc.contributor.authorGabau, E
dc.contributor.authorVetro, A
dc.contributor.authorGuerrini, R
dc.contributor.authorBakhtiari, S
dc.contributor.authorKruer, MC
dc.contributor.authorAmor, DJ
dc.contributor.authorCooper, MS
dc.contributor.authorBijlsma, EK
dc.contributor.authorBarakat, TS
dc.contributor.authorvan Dooren, MF
dc.contributor.authorvan Slegtenhorst, M
dc.contributor.authorPfundt, R
dc.contributor.authorGilissen, C
dc.contributor.authorWillemsen, MA
dc.contributor.authorde Vries, BBA
dc.contributor.authorde Brouwer, APM
dc.contributor.authorKoolen, DA
dc.identifierpii: 10.1038/s41436-019-0703-y
dc.identifier.citationSa, M. J. N., Venselaar, H., Wiel, L., Trimouille, A., Lasseaux, E., Naudion, S., Lacombe, D., Piton, A., Vincent-Delorme, C., Zweier, C., Reis, A., Trollmann, R., Ruiz, A., Gabau, E., Vetro, A., Guerrini, R., Bakhtiari, S., Kruer, M. C., Amor, D. J. ,... Koolen, D. A. (2020). De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy. GENETICS IN MEDICINE, 22 (4), pp.797-802.
dc.description.abstractPURPOSE: To delineate the genotype-phenotype correlation in individuals with likely pathogenic variants in the CLTC gene. METHODS: We describe 13 individuals with de novo CLTC variants. Causality of variants was determined by using the tolerance landscape of CLTC and computer-assisted molecular modeling where applicable. Phenotypic abnormalities observed in the individuals identified with missense and in-frame variants were compared with those with nonsense or frameshift variants in CLTC. RESULTS: All de novo variants were judged to be causal. Combining our data with that of 14 previously reported affected individuals (n = 27), all had intellectual disability (ID), ranging from mild to moderate/severe, with or without additional neurologic, behavioral, craniofacial, ophthalmologic, and gastrointestinal features. Microcephaly, hypoplasia of the corpus callosum, and epilepsy were more frequently observed in individuals with missense and in-frame variants than in those with nonsense and frameshift variants. However, this difference was not significant. CONCLUSIONS: 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.
dc.titleDe novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy
dc.typeJournal Article
melbourne.affiliation.departmentPaediatrics (RCH)
melbourne.source.titleGenetics in Medicine
melbourne.openaccess.statusAccepted version
melbourne.contributor.authorAmor, David
melbourne.contributor.authorCooper, Monica
melbourne.accessrightsAccess this item via the Open Access location

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