مورد إلكتروني
De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy
| العنوان: | De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy |
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| المؤلفون: | Sa, MJN, 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, MC, Amor, DJ, Cooper, MS, Bijlsma, EK, Barakat, TS, van Dooren, MF, van Slegtenhorst, M, Pfundt, R, Gilissen, C, Willemsen, MA, de Vries, BBA, de Brouwer, APM, Koolen, DA |
| بيانات النشر: | NATURE PUBLISHING GROUP 2020-04-01 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | 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. |
| مصطلحات الفهرس: | Journal Article |
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| الإتاحة: | Open access content. Open access content |
| أرقام أخرى: | UMV oai:jupiter.its.unimelb.edu.au:11343/253974 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. 10.1038/s41436-019-0703-y 1530-0366 1098-3600 1315728089 |
| المصدر المساهم: | UNIV OF MELBOURNE From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1315728089 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |