Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome
Abstract
We show that haploinsufficiency of KANSL1 is sufficient to cause the 17q21.31 microdeletion syndrome, a multisystem disorder characterized by intellectual disability, hypotonia and distinctive facial features. The KANSL1 protein is an evolutionarily conserved regulator of the chromatin modifier KAT8, which influences gene expression through histone H4 lysine 16 (H4K16) acetylation. RNA sequencing studies in cell lines derived from affected individuals and the presence of learning deficits in Drosophila melanogaster mutants suggest a role for KANSL1 in neuronal processes.
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Mutations in KANSL1 cause 17q21.31 microdeletion syndrome, a condition with ID as a characteristic feature.
“were recently found to underlie 17q21.31 microdeletion syndrome, in which ID is a characteristic feature [77]”
From A de novo convergence of autism genetics and molecular neuroscience (2014) · cites this paper as [77]
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- Authors
- Koolen, D. A., Kramer, J. M., Neveling, K., Nillesen, W. M., Moore-Barton, H. L., Elmslie, F. V., Toutain, A., Amiel, J., Malan, V., Tsai, A. C.-H., Cheung, S. W., Gilissen, C., Verwiel, E. T. P., Martens, S., Feuth, T., Bongers, E. M. H. F., de Vries, P., Scheffer, H., Vissers, L. E. L. M., de Brouwer, A. P. M., Brunner, H. G., Veltman, J. A., Schenck, A., Yntema, H. G., & de Vries, B. B. A.
- Affiliations
- Radboud University Nijmegen (NL)
- St George's, University of London (GB)
- Centre Hospitalier Universitaire de Tours (FR)
- Hôpital Necker-Enfants Malades (FR)
- Children's Hospital Colorado (US)
- Baylor College of Medicine (US)
- ORCID
- Venue
- Nature Genetics
- Published
- 2012-04-29
- Volume
- 44
- Issue
- 6
- Pages
- 639-641
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2058601962
- Cited by
- 232
- References
- 14
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 11 · 2023: 20 · 2022: 14 · 2021: 20 · 2020: 22 · 2019: 15 · 2018: 11 · 2017: 18 · 2016: 18 · 2015: 16 · 2014: 23 · 2013: 18 · 2012: 5
- FWCI
- 11.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- KANSL1, haploinsufficiency, chromatin regulation, KAT8, H4K16ac, intellectual disability, hypotonia, facial dysmorphism, learning deficits, Drosophila melanogaster, gene expression
- MeSH terms
- Abnormalities, Multiple, Aged, Aging, Chromosome Deletion, Chromosomes, Human, Pair 17, Female, Humans, Male, Intellectual Disability, Middle Aged, Mutation, Nuclear Proteins, Syndrome, Facies, Haploinsufficiency, Smith-Magenis Syndrome
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