CDKL5 variants
| العنوان: | CDKL5 variants |
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| المؤلفون: | Judith Armstrong, Stuart Cobb, Mercedes Pineda, Friederike Hennig, Mark E.S. Bailey, Jenny Downs, Helen Leonard, Tim A. Benke, Angus John Clarke, Vera M. Kalscheuer, Ralph D. Hector |
| المصدر: | NEUROLOGY-GENETICS r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu Fundació Sant Joan de Déu Neurology Genetics r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu instname Hector, R D, Kalscheuer, V M, Hennig, F, Leonard, H, Downs, J, Clarke, A, Benke, T A, Armstrong, J, Pineda, M, Bailey, M E S & Cobb, S R 2017, ' CDKL5 variants: improving our understanding of a rare neurological disorder ', Neurology Genetics, vol. 3, no. 6 . https://doi.org/10.1212/NXG.0000000000000200Test |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, education.field_of_study, Population, CDKL5, Computational biology, Disease, Biology, 03 medical and health sciences, Exon, 030104 developmental biology, 0302 clinical medicine, RNA splicing, Genetic variation, Missense mutation, Neurology (clinical), education, Gene, 030217 neurology & neurosurgery, Genetics (clinical) |
| الوصف: | Objective:To provide new insights into the interpretation of genetic variants in a rare neurologic disorder, CDKL5 deficiency, in the contexts of population sequencing data and an updated characterization of the CDKL5 gene.Methods:We analyzed all known potentially pathogenic CDKL5 variants by combining data from large-scale population sequencing studies with CDKL5 variants from new and all available clinical cohorts and combined this with computational methods to predict pathogenicity.Results:The study has identified several variants that can be reclassified as benign or likely benign. With the addition of novel CDKL5 variants, we confirm that pathogenic missense variants cluster in the catalytic domain of CDKL5 and reclassify a purported missense variant as having a splicing consequence. We provide further evidence that missense variants in the final 3 exons are likely to be benign and not important to disease pathology. We also describe benign splicing and nonsense variants within these exons, suggesting that isoform hCDKL5_5 is likely to have little or no neurologic significance. We also use the available data to make a preliminary estimate of minimum incidence of CDKL5 deficiency.Conclusions:These findings have implications for genetic diagnosis, providing evidence for the reclassification of specific variants previously thought to result in CDKL5 deficiency. Together, these analyses support the view that the predominant brain isoform in humans (hCDKL5_1) is crucial for normal neurodevelopment and that the catalytic domain is the primary functional domain. |
| وصف الملف: | application/pdf |
| تدمد: | 2376-7839 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ac1d259bccaf2c1cb0284876ef3a3c4Test https://doi.org/10.1212/nxg.0000000000000200Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9ac1d259bccaf2c1cb0284876ef3a3c4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23767839 |
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