Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome

David A. Koolen, Jamie M. Kramer, Kornelia Neveling, Willy M. Nillesen, Heather L. Moore-Barton, Frances V. Elmslie, Annick Toutain, Jeanne Amiel, Valérie Malan, Anne Tsai, Sau Wai Cheung, Christian Gilissen, Eugene T P Verwiel, Sarah Martens, Ton Feuth, Ernie M H F Bongers, Petra De Vries, Hans Scheffer, Lisenka E L M Vissers, Arjan P M De BrouwerHan G. Brunner, Joris A. Veltman, Annette Schenck, Helger G. Yntema, Bert B A De Vries

Research output: Contribution to journalArticle

109 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)639-641
Number of pages3
JournalNature Genetics
Volume44
Issue number6
DOIs
StatePublished - Jun 2012
Externally publishedYes

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Modifier Genes
RNA Sequence Analysis
Haploinsufficiency
Muscle Hypotonia
Acetylation
Drosophila melanogaster
Intellectual Disability
Histones
Lysine
Chromatin
Learning
Gene Expression
Cell Line
Mutation
Proteins
Chromosome 17q21.31 Deletion Syndrome

ASJC Scopus subject areas

  • Genetics

Cite this

Koolen, D. A., Kramer, J. M., Neveling, K., Nillesen, W. M., Moore-Barton, H. L., Elmslie, F. V., ... De Vries, B. B. A. (2012). Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome. Nature Genetics, 44(6), 639-641. https://doi.org/10.1038/ng.2262

Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome. / Koolen, David A.; Kramer, Jamie M.; Neveling, Kornelia; Nillesen, Willy M.; Moore-Barton, Heather L.; Elmslie, Frances V.; Toutain, Annick; Amiel, Jeanne; Malan, Valérie; Tsai, Anne; Cheung, Sau Wai; Gilissen, Christian; Verwiel, Eugene T P; Martens, Sarah; Feuth, Ton; Bongers, Ernie M H F; De Vries, Petra; Scheffer, Hans; Vissers, Lisenka E L M; De Brouwer, Arjan P M; Brunner, Han G.; Veltman, Joris A.; Schenck, Annette; Yntema, Helger G.; De Vries, Bert B A.

In: Nature Genetics, Vol. 44, No. 6, 06.2012, p. 639-641.

Research output: Contribution to journalArticle

Koolen, DA, Kramer, JM, Neveling, K, Nillesen, WM, Moore-Barton, HL, Elmslie, FV, Toutain, A, Amiel, J, Malan, V, Tsai, A, Cheung, SW, Gilissen, C, Verwiel, ETP, Martens, S, Feuth, T, Bongers, EMHF, De Vries, P, Scheffer, H, Vissers, LELM, De Brouwer, APM, Brunner, HG, Veltman, JA, Schenck, A, Yntema, HG & De Vries, BBA 2012, 'Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome', Nature Genetics, vol. 44, no. 6, pp. 639-641. https://doi.org/10.1038/ng.2262
Koolen DA, Kramer JM, Neveling K, Nillesen WM, Moore-Barton HL, Elmslie FV et al. Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome. Nature Genetics. 2012 Jun;44(6):639-641. https://doi.org/10.1038/ng.2262
Koolen, David A. ; Kramer, Jamie M. ; Neveling, Kornelia ; Nillesen, Willy M. ; Moore-Barton, Heather L. ; Elmslie, Frances V. ; Toutain, Annick ; Amiel, Jeanne ; Malan, Valérie ; Tsai, Anne ; Cheung, Sau Wai ; Gilissen, Christian ; Verwiel, Eugene T P ; Martens, Sarah ; Feuth, Ton ; Bongers, Ernie M H F ; De Vries, Petra ; Scheffer, Hans ; Vissers, Lisenka E L M ; De Brouwer, Arjan P M ; Brunner, Han G. ; Veltman, Joris A. ; Schenck, Annette ; Yntema, Helger G. ; De Vries, Bert B A. / Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome. In: Nature Genetics. 2012 ; Vol. 44, No. 6. pp. 639-641.
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