Inherited variants in CHD3 show variable expressivity in Snijders Blok-Campeau syndrome
| العنوان: | Inherited variants in CHD3 show variable expressivity in Snijders Blok-Campeau syndrome |
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| المؤلفون: | Jet van der Spek, Joery den Hoed, Lot Snijders Blok, Alexander J.M. Dingemans, Dick Schijven, Christoffer Nellaker, Hanka Venselaar, Galuh D.N. Astuti, Tahsin Stefan Barakat, E. Martina Bebin, Stefanie Beck-Wödl, Gea Beunders, Natasha J. Brown, Theresa Brunet, Han G. Brunner, Philippe M. Campeau, Goran Čuturilo, Christian Gilissen, Tobias B. Haack, Irina Hüning, Ralf A. Husain, Benjamin Kamien, Sze Chern Lim, Luca Lovrecic, Janine Magg, Ales Maver, Valancy Miranda, Danielle C. Monteil, Charlotte W. Ockeloen, Lynn S. Pais, Vasilica Plaiasu, Laura Raiti, Christopher Richmond, Angelika Rieß, Eva M.C. Schwaibold, Marleen E.H. Simon, Stephanie Spranger, Tiong Yang Tan, Michelle L. Thompson, Bert B.A. de Vries, Ella J. Wilkins, Marjolein H. Willemsen, Clyde Francks, Lisenka E.L.M. Vissers, Simon E. Fisher, Tjitske Kleefstra |
| المساهمون: | Clinical Genetics, MUMC+: DA Klinische Genetica (5), Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine |
| المصدر: | Genetics in Medicine, 24(6), 1283-1296. Lippincott Williams & Wilkins Genetics in Medicine, 24(6), 1283-1296. Nature Publishing Group Genetics in Medicine, 24, 1283-1296 Genetics in Medicine, 24, 6, pp. 1283-1296 Genetics in Medicine |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Neuroinformatics, Heterozygote, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], DNA Helicases, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Syndrome, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], CHD3, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Reduced penetrance, Phenotype, All institutes and research themes of the Radboud University Medical Center, RARE, SDG 3 - Good Health and Well-being, Neurodevelopmental disorder, Neurodevelopmental Disorders, Variable expressivity, Humans, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Genetics (clinical), Mi-2 Nucleosome Remodeling and Deacetylase Complex, Inherited variants |
| الوصف: | PURPOSE: Common diagnostic next-generation sequencing strategies are not optimized to identify inherited variants in genes associated with dominant neurodevelopmental disorders as causal when the transmitting parent is clinically unaffected, leaving a significant number of cases with neurodevelopmental disorders undiagnosed.METHODS: We characterized 21 families with inherited heterozygous missense or protein-truncating variants in CHD3, a gene in which de novo variants cause Snijders Blok-Campeau syndrome.RESULTS: Computational facial and Human Phenotype Ontology-based comparisons showed that the phenotype of probands with inherited CHD3 variants overlaps with the phenotype previously associated with de novo CHD3 variants, whereas heterozygote parents are mildly or not affected, suggesting variable expressivity. In addition, similarly reduced expression levels of CHD3 protein in cells of an affected proband and of healthy family members with a CHD3 protein-truncating variant suggested that compensation of expression from the wild-type allele is unlikely to be an underlying mechanism. Notably, most inherited CHD3 variants were maternally transmitted.CONCLUSION: Our results point to a significant role of inherited variation in Snijders Blok-Campeau syndrome, a finding that is critical for correct variant interpretation and genetic counseling and warrants further investigation toward understanding the broader contributions of such variation to the landscape of human disease. |
| وصف الملف: | application/pdf; application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
| اللغة: | English |
| تدمد: | 1098-3600 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6c634fbbfbfe9fc61dcffebf9b78acf3Test https://doi.org/10.1016/j.gim.2022.02.014Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6c634fbbfbfe9fc61dcffebf9b78acf3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10983600 |
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