A recurrent synonymous KAT6B mutation causes Say‐Barber‐Biesecker/Young‐Simpson syndrome by inducing aberrant splicing
Open accessAbstract
Mutations of the histone acetyltransferase‐encoding KAT6B gene cause the Say‐Barber‐Biesecker/Young‐Simpson (SBBYS) type of blepharophimosis‐“mental retardation” syndromes and the more severe genitopatellar syndrome. The SBBYS syndrome‐causing mutations are clustered in the large exon 18 of KAT6B and almost exclusively lead to predicted protein truncation. An atypical KAT6B mutation, a de novo synonymous variant located in exon 16 (c.3147G>A, p.(Pro1049Pro)) was previously identified in three unrelated patients. This exonic mutation was predicted in silico to cause protein truncation through aberrant splicing. Here, we report three additional unrelated children with typical SBBYS syndrome and the KAT6B c.3147G>A mutation. We show on RNA derived from patient blood that the mutation indeed induces aberrant splicing through the use of a cryptic exonic splice acceptor site created by the sequence variant. Our results thus identify the synonymous variant c.3147G>A as a splice site mutation and a mutational hot spot in SBBYS syndrome. © 2015 Wiley Periodicals, Inc.
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The synonymous SpliceAI enrichment corresponds to about 15 excess splice-disrupting synonymous de novo mutations, six of which are accounted for by a recurrent KAT6B synonymous mutation.
“This enrichment corresponds to an excess of ~15 splice-disrupting synonymous DNMs in our cohort, of which six are accounted for by a recurrent synonymous DNM in KAT6B known to disrupt splicing14.”
From Evidence for 28 genetic disorders discovered by combining healthcare and research data (2020) · cites this paper as [14]
Cites
The CpG dinucleotide and human genetic disease
Cooper, D. N., & Youssoufian, H. (1988) · Human Genetics · doi:10.1007/bf00278187 · Cited by 936 · see citing works
Clayton‐Smith, J., O’Sullivan, J., Daly, S. B., Bhaskar, S. S., Day, R., Anderson, B., Voss, A. K., Thomas, T., Biesecker, L. G., Smith, P., et al. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.10.008 · Cited by 184 · see citing works
Self-citationMutations in KAT6B, Encoding a Histone Acetyltransferase, Cause Genitopatellar Syndrome
Campeau, P. M., Kim, J. C., Lu, J. T., Schwartzentruber, J., Abdul-Rahman, O. A., Schlaubitz, S., Murdock, D. M., Jiang, M., Lammer, E. J., Enns, G. M., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.023 · Cited by 137 · see citing works
Simpson, M. A., Deshpande, C., Dafou, D., Vissers, L. E. L. M., Woollard, W. J., Holder, S., Gillessen‐Kaesbach, G., Derks, R. C., White, S. M., Cohen‐Snuijf, R., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.024 · Cited by 103 · see citing works
Campeau, P. M., Lu, J. T., Dawson, B., Fokkema, I. F. A. C., Robertson, S. P., Gibbs, R. A., & Lee, B. (2012) · Human Mutation · doi:10.1002/humu.22141 · Cited by 85 · see citing works
Further delineation of the KAT6B molecular and phenotypic spectrum
study, D., Gannon, T., Perveen, R., Schlecht, H., Ramsden, S., Anderson, B., Kerr, B. A., Day, R., Banka, S., Suri, M., et al. (2014) · European Journal of Human Genetics · doi:10.1038/ejhg.2014.248 · Cited by 65 · see citing works
Self-citationSzakszon, K., Salpietro, C. D., Kakar, N., Knegt, A. C., Oláh, É., Dallapiccola, B., & Borck, G. (2013) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.35848 · Cited by 44 · see citing works
Self-citationYu, H., Geiger, E. A., Medne, L., Zackai, E. H., & Shaikh, T. H. (2014) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36379 · Cited by 39 · see citing works
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Evidence for 28 genetic disorders discovered by combining healthcare and research data
Kaplanis, J., Samocha, K. E., Wiel, L., Zhang, Z., Arvai, K. J., Eberhardt, R. Y., Gallone, G., Lelieveld, S. H., Martin, H. C., McRae, J. F., et al. (2020) · Nature · doi:10.1038/s41586-020-2832-5 · Cited by 615 · see citing works
Self-citationKaplanis, J., Samocha, K. E., Wiel, L., Zhang, Z., Arvai, K. J., Eberhardt, R. Y., Gallone, G., Lelieveld, S. H., Martin, H. C., McRae, J. F., et al. (2019) · doi:10.1101/797787 · Cited by 36 · see citing works
Lin‐Gettig syndrome: Craniosynostosis expands the spectrum of the <i>KAT6B</i> related disorders
Bashir, R. A., Dixit, A., Goedhart, C., Parboosingh, J. S., Innes, A. M., Care for Rare Canada Consortium, Ferreira, P., Hasan, S. U., & Au, P. B. (2017) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.38355 · Cited by 21 · see citing works
- Authors
- Yilmaz, R., Beleza‐Meireles, A., Price, S., Oliveira, R., Kubisch, C., Clayton‐Smith, J., Szakszon, K., & Borck, G.
- Affiliations
- Universität Ulm (DE)
- Guy's Hospital (GB)
- Northampton General Hospital (GB)
- Unidade Local de Saúde de Coimbra (PT)
- University Medical Center Hamburg-Eppendorf (DE)
- St Mary's Hospital (GB)
- University of Debrecen (HU)
- Corresponding author
- Borck, Guntram
- ORCID
- Venue
- American Journal of Medical Genetics Part A
- Publisher
- Wiley
- Published
- 2015-09-03
- Volume
- 167
- Issue
- 12
- Pages
- 3006-3010
- ISSN
- 1552-4825 (ISSN-L)
- 1552-4833
- OpenAlex
- W1913135618
- Cited by
- 22
- References
- 8
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 1 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 4 · 2016: 2
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- American Journal of Medical Genetics Part A (publishedVersion)
- PubMed (publishedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
- Funders
- Universität Ulm
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
- Keywords
- KAT6B, synonymous mutations, aberrant splicing, histone acetyltransferase, de novo mutations, mutational hotspots, exon 16
- MeSH terms
- Child, Child, Preschool, Congenital Hypothyroidism, Female, Heart Defects, Congenital, Humans, Joint Instability, Male, Intellectual Disability, Mutation, Pregnancy, RNA Splicing, Blepharophimosis, Facies, RNA Splice Sites, Histone Acetyltransferases
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