The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
KAT6A Syndrome: genotype–phenotype correlation in 76 patients with pathogenic KAT6A variants
Open accessAbstract
Purpose Pathogenic variants in KAT6A have recently been identified as a cause of syndromic developmental delay. Within 2 years, the number of patients identified with pathogenic KAT6A variants has rapidly expanded and the full extent and variability of the clinical phenotype has not been reported.Methods We obtained data for patients with KAT6A pathogenic variants through three sources: treating clinicians, an online family survey distributed through social media, and a literature review.Results We identified 52 unreported cases, bringing the total number of published cases to 76. Our results expand the genotypic spectrum of pathogenic variants to include missense and splicing mutations. We functionally validated a pathogenic splice-site variant and identified a likely hotspot location for de novo missense variants. The majority of clinical features in KAT6A syndrome have highly variable penetrance. For core features such as intellectual disability, speech delay, microcephaly, cardiac anomalies, and gastrointestinal complications, genotype- phenotype correlations show that late-truncating pathogenic variants (exons 16-17) are significantly more prevalent. We highlight novel associations, including an increased risk of gastrointestinal obstruction.Conclusion Our data expand the genotypic and phenotypic spectrum for individuals with genetic pathogenic variants in KAT6A and we outline appropriate clinical management.
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“Interactions between researchers and families with rare disease have enabled natural history studies to be driven by family support groups positioned to initiate data collection from patient cohorts once a causal gene is discovered20.”
From A brief history of human disease genetics (2020) · cites this paper as [20]
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The key roles of the lysine acetyltransferases KAT6A and KAT6B in physiology and pathology
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Metadata
- Authors
- Kennedy, J., Goudie, D., Blair, E., Chandler, K., Joss, S., McKay, V., Green, A., Armstrong, R., Lees, M., Kamien, B., Hopper, B., Tan, T. Y., Yap, P., Stark, Z., Okamoto, N., Miyake, N., Matsumoto, N., Macnamara, E., Murphy, J. L., McCormick, E., Hakonarson, H., Falk, M. J., Li, D., Blackburn, P., Klee, E., Babovic-Vuksanovic, D., Schelley, S., Hudgins, L., Kant, S., Isidor, B., Cogne, B., Bradbury, K., Williams, M., Patel, C., Heussler, H., Duff-Farrier, C., Lakeman, P., Scurr, I., Kini, U., Elting, M., Reijnders, M., Schuurs-Hoeijmakers, J., Wafik, M., Blomhoff, A., Ruivenkamp, C. A. L., Nibbeling, E., Dingemans, A. J. M., Douine, E. D., Nelson, S. F., Hempel, M., Bierhals, T., Lessel, D., Johannsen, J., Arboleda, V. A., & Newbury-Ecob, R.
- Affiliations
- University Hospitals Bristol NHS Foundation Trust (GB)
- Ninewells Hospital (GB)
- Churchill Hospital (GB)
- Manchester Academic Health Science Centre (GB)
- Queen Elizabeth University Hospital (GB)
- Liverpool Women's Hospital (GB)
- University College Dublin (IE)
- Addenbrooke's Hospital (GB)
- Great Ormond Street Hospital (GB)
- Hunter Genetics (AU)
- The University of Melbourne (AU)
- Victorian Clinical Genetics Services (AU)
- Osaka Women's and Children's Hospital (JP)
- Yokohama City University (JP)
- National Institutes of Health (US)
- Children's Hospital of Philadelphia (US)
- Mayo Clinic (US)
- Stanford University (US)
- Leiden University Medical Center (NL)
- Centre Hospitalier Universitaire de Nantes (FR)
- Guy's Hospital (GB)
- Queensland Health (AU)
- Children's Health Queensland Hospital and Health Service (AU)
- Amsterdam UMC Location University of Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Radboud University Medical Center (NL)
- Oslo University Hospital (NO)
- Leiden University (NL)
- University of Groningen (NL)
- University of California, Los Angeles (US)
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Arboleda, Valerie A.
- ORCID
- Kennedy, Joanna
- Joss, Shelagh
- McKay, Victoria
- Green, Andrew
- Armstrong, Ruth
- Lees, Melissa
- Kamien, Benjamin
- Tan, Tiong Yang
- Yap, Patrick
- Stark, Zornitza
- Okamoto, Nobuhiko
- Miyake, Noriko
- Matsumoto, Naomichi
- Macnamara, Ellen
- Murphy, Jennifer L.
- McCormick, Elizabeth
- Hakonarson, Hakon
- Falk, Marni J.
- Blackburn, Patrick
- Klee, Eric
- Schelley, Susan
- Hudgins, Louanne
- Kant, Sarina
- Isidor, Bertrand
- Williams, Mark
- Patel, Chirag
- Heussler, Helen
- Lakeman, Phillis
- Kini, Usha
- Elting, Mariet
- Reijnders, Margot
- Schuurs-Hoeijmakers, Janneke
- Wafik, Mohamed
- Ruivenkamp, Claudia A.L.
- Nibbeling, Esther
- Dingemans, Alexander J.M.
- Douine, Emilie D.
- Nelson, Stanley F.
- Hempel, Maja
- Bierhals, Tatjana
- Lessel, Davor
- Johannsen, Jessika
- Arboleda, Valerie A.
- Newbury-Ecob, Ruth
- Venue
- Genetics in Medicine
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 21
- Issue
- 4
- Pages
- 850-860
- ISSN
- 1098-3600 (ISSN-L)
- PMC
- PMC6634310
- OpenAlex
- W2890142544
- Cited by
- 107
- References
- 35
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 18 · 2023: 17 · 2022: 17 · 2021: 16 · 2020: 16 · 2019: 1
- FWCI
- 5.06
- Type
- journal article
- Language
- en
- Update notices
- erratum (2020-11-01)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Genetics in Medicine (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- PubMed Central (acceptedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Funders
- Wellcome Trust (HICF-1009-003, GEN/284/12, WT 098051, 10/H0305/83)
- National Institute for Health and Care Research (10/H0305/83, HICF-1009-003, WT098051)
- National Institutes of Health (DP5OD024579)
- Japan Society for the Promotion of Science (17H01539, 16H05357)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD086984)
- 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 › Genomic variations and chromosomal abnormalities
- Keywords
- genotype-phenotype correlation, intellectual disability, speech delay, microcephaly, cardiac anomalies, gastrointestinal obstruction, splice site mutation, missense mutations, de novo mutations, penetrance, phenotypic variability
- MeSH terms
- Adolescent, Adult, Child, Developmental Disabilities, Child, Preschool, Chromosome Deletion, Female, Genotype, Humans, Infant, Male, Intellectual Disability, Microcephaly, Mutation, Phenotype, Protein Isoforms, Histone Acetyltransferases, Young Adult, Genetic Association Studies, Exome
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