De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy
dc.contributor.author | Sa, MJN | |
dc.contributor.author | Venselaar, H | |
dc.contributor.author | Wiel, L | |
dc.contributor.author | Trimouille, A | |
dc.contributor.author | Lasseaux, E | |
dc.contributor.author | Naudion, S | |
dc.contributor.author | Lacombe, D | |
dc.contributor.author | Piton, A | |
dc.contributor.author | Vincent-Delorme, C | |
dc.contributor.author | Zweier, C | |
dc.contributor.author | Reis, A | |
dc.contributor.author | Trollmann, R | |
dc.contributor.author | Ruiz, A | |
dc.contributor.author | Gabau, E | |
dc.contributor.author | Vetro, A | |
dc.contributor.author | Guerrini, R | |
dc.contributor.author | Bakhtiari, S | |
dc.contributor.author | Kruer, MC | |
dc.contributor.author | Amor, DJ | |
dc.contributor.author | Cooper, MS | |
dc.contributor.author | Bijlsma, EK | |
dc.contributor.author | Barakat, TS | |
dc.contributor.author | van Dooren, MF | |
dc.contributor.author | van Slegtenhorst, M | |
dc.contributor.author | Pfundt, R | |
dc.contributor.author | Gilissen, C | |
dc.contributor.author | Willemsen, MA | |
dc.contributor.author | de Vries, BBA | |
dc.contributor.author | de Brouwer, APM | |
dc.contributor.author | Koolen, DA | |
dc.date.accessioned | 2020-12-14T05:41:04Z | |
dc.date.available | 2020-12-14T05:41:04Z | |
dc.date.issued | 2020-04-01 | |
dc.identifier | pii: 10.1038/s41436-019-0703-y | |
dc.identifier.citation | Sa, 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. https://doi.org/10.1038/s41436-019-0703-y. | |
dc.identifier.issn | 1098-3600 | |
dc.identifier.uri | http://hdl.handle.net/11343/253974 | |
dc.description.abstract | PURPOSE: 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.language | English | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.title | De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy | |
dc.type | Journal Article | |
dc.identifier.doi | 10.1038/s41436-019-0703-y | |
melbourne.affiliation.department | Paediatrics (RCH) | |
melbourne.affiliation.department | ||
melbourne.source.title | Genetics in Medicine | |
melbourne.source.volume | 22 | |
melbourne.source.issue | 4 | |
melbourne.source.pages | 797-802 | |
melbourne.elementsid | 1424826 | |
melbourne.openaccess.url | https://repository.arizona.edu/bitstream/10150/641161/1/2019_10_01-CLTC_Genotype-Phenotype.pdf | |
melbourne.openaccess.status | Accepted version | |
melbourne.contributor.author | Amor, David | |
melbourne.contributor.author | Cooper, Monica | |
dc.identifier.eissn | 1530-0366 | |
melbourne.accessrights | Access this item via the Open Access location |
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