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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.date.accessioned2020-12-14T05:41:04Z
dc.date.available2020-12-14T05:41:04Z
dc.date.issued2020-04-01
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. https://doi.org/10.1038/s41436-019-0703-y.
dc.identifier.issn1098-3600
dc.identifier.urihttp://hdl.handle.net/11343/253974
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.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
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
dc.identifier.doi10.1038/s41436-019-0703-y
melbourne.affiliation.departmentPaediatrics (RCH)
melbourne.affiliation.department
melbourne.source.titleGenetics in Medicine
melbourne.source.volume22
melbourne.source.issue4
melbourne.source.pages797-802
melbourne.elementsid1424826
melbourne.openaccess.urlhttps://repository.arizona.edu/bitstream/10150/641161/1/2019_10_01-CLTC_Genotype-Phenotype.pdf
melbourne.openaccess.statusAccepted version
melbourne.contributor.authorAmor, David
melbourne.contributor.authorCooper, Monica
dc.identifier.eissn1530-0366
melbourne.accessrightsAccess this item via the Open Access location


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