Evidence map›Paper›PMID 27939640›Full record

ArticleAmerican journal of human genetics2017

Mutations in the Chromatin Regulator Gene BRPF1 Cause Syndromic Intellectual Disability and Deficient Histone Acetylation.

Kezhi Yan, Justine Rousseau, Rebecca Okashah Littlejohn, Courtney Kiss, Anna Lehman, Jill A Rosenfeld, Constance T R Stumpel, Alexander P A Stegmann, Laurie Robak, Fernando Scaglia and 26 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 103 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors at 11 institutions in 4 countries.

Kezhi YanRosalind & Morris Goodman Cancer Research Center and Department of Medicine, McGill University, Montreal, QC H3A 1A3, Canada.
Justine RousseauCHUSJ Research Center, CHU Sainte-Justine, Montreal, QC H3T 1J4, Canada.
Rebecca Okashah LittlejohnDepartment of Pediatrics, Baylor College of Medicine, San Antonio, TX 77030, USA.
Courtney KissKingston General Hospital, 76 Stuart Street, Armstrong 4, Kingston, ON K7L 2V7, Canada.
Anna LehmanDepartment of Medical Genetics, University of British Columbia, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada.
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Constance T R StumpelDepartment of Clinical Genetics and School for Oncology & Developmental Biology, Maastricht University Medical Center, Maastricht 6229, the Netherlands.
Alexander P A StegmannDepartment of Clinical Genetics and School for Oncology & Developmental Biology, Maastricht University Medical Center, Maastricht 6229, the Netherlands.
Laurie RobakDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Fernando ScagliaDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Thi Tuyet Mai NguyenCHUSJ Research Center, CHU Sainte-Justine, Montreal, QC H3T 1J4, Canada.
He FuCHUSJ Research Center, CHU Sainte-Justine, Montreal, QC H3T 1J4, Canada.
Norbert F AjeawungCHUSJ Research Center, CHU Sainte-Justine, Montreal, QC H3T 1J4, Canada.
Maria Vittoria CamurriCHUSJ Research Center, CHU Sainte-Justine, Montreal, QC H3T 1J4, Canada.
Lin LiRosalind & Morris Goodman Cancer Research Center and Department of Medicine, McGill University, Montreal, QC H3A 1A3, Canada.
Alice GardhamNorth West Thames Regional Genetics Service, London North West Healthcare NHS Trust, Northwick Park Hospital, Watford Road, Harrow HA1 3UJ, UK.
Bianca PanisDepartment of Pediatrics, Zuyderland Medical Center, Heerlen and Sittard 6419, the Netherlands.
Mohammed AlmannaiDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Maria J Guillen SacotoGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Berivan BaskinGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Claudia RuivenkampDepartment of Clinical Genetics, Leiden University Medical Center, Leiden 2300RC, the Netherlands.
Fan XiaDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Weimin BiDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
DDD StudyDecipher Developmental Disorder Study, Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UK.
CAUSES StudyDepartment of Medical Genetics, University of British Columbia, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada.
Megan T ChoGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Thomas P PotjerDepartment of Clinical Genetics, Leiden University Medical Center, Leiden 2300RC, the Netherlands.
Gijs W E SantenDepartment of Clinical Genetics, Leiden University Medical Center, Leiden 2300RC, the Netherlands.
Michael J ParkerSheffield Clinical Genetics Service, OPD2, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK.
Natalie CanhamNorth West Thames Regional Genetics Service, London North West Healthcare NHS Trust, Northwick Park Hospital, Watford Road, Harrow HA1 3UJ, UK.
Margaret McKinnonDepartment of Medical Genetics, University of British Columbia, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada.
Lorraine PotockiDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Jennifer J MacKenzieKingston General Hospital, 76 Stuart Street, Armstrong 4, Kingston, ON K7L 2V7, Canada; Division of Clinical Genetics, Department of Pediatrics, McMaster University, Hamilton, ON L8S 4K1, Canada.
Elizabeth R RoederDepartment of Pediatrics, Baylor College of Medicine, San Antonio, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Philippe M CampeauCHUSJ Research Center, CHU Sainte-Justine, Montreal, QC H3T 1J4, Canada; Department of Pediatrics, Sainte-Justine Hospital and University of Montreal, QC H3T 1J4, Canada. Electronic address: p.campeau@umontreal.ca.
Xiang-Jiao YangRosalind & Morris Goodman Cancer Research Center and Department of Medicine, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University and McGill University Health Center, Montreal, QC H3A 1A3, Canada. Electronic address: xiang-jiao.yang@mcgill.ca.
Baylor College of Medicine · USCentre Hospitalier Universitaire Sainte-Justine · CALeiden University Medical Center · NLMcGill University · CALondon North West Healthcare NHS Trust · GBMaastricht University · NLUniversity of British Columbia · CAKingston General Hospital · CAMcMaster University · CANorthern General Hospital · GBZuyderland Medisch Centrum · NL

Funding

Wellcome Trust
6 · The paper itself

Abstract

Identification of over 500 epigenetic regulators in humans raises an interesting question regarding how chromatin dysregulation contributes to different diseases. Bromodomain and PHD finger-containing protein 1 (BRPF1) is a multivalent chromatin regulator possessing three histone-binding domains, one non-specific DNA-binding module, and several motifs for interacting with and activating three lysine acetyltransferases. Genetic analyses of fish brpf1 and mouse Brpf1 have uncovered an important role in skeletal, hematopoietic, and brain development, but it remains unclear how BRPF1 is linked to human development and disease. Here, we describe an intellectual disability disorder in ten individuals with inherited or de novo monoallelic BRPF1 mutations. Symptoms include infantile hypotonia, global developmental delay, intellectual disability, expressive language impairment, and facial dysmorphisms. Central nervous system and spinal abnormalities are also seen in some individuals. These clinical features overlap with but are not identical to those reported for persons with KAT6A or KAT6B mutations, suggesting that BRPF1 targets these two acetyltransferases and additional partners in humans. Functional assays showed that the resulting BRPF1 variants are pathogenic and impair acetylation of histone H3 at lysine 23, an abundant but poorly characterized epigenetic mark. We also found a similar deficiency in different lines of Brpf1-knockout mice. These data indicate that aberrations in the chromatin regulator gene BRPF1 cause histone H3 acetylation deficiency and a previously unrecognized intellectual disability syndrome.

Indexed as

MutationAcetylationAdaptor Proteins, Signal TransducingAdolescentAllelesAnimalsBromodomain Containing ProteinsCarrier ProteinsChildChromatinDevelopmental DisabilitiesDNA-Binding ProteinsFaceFemaleHistone AcetyltransferasesHistonesAdaptor Proteins, Signal TransducingBromodomain Containing ProteinsBRPF1 protein, humanBRPF1 protein, mouseCarrier ProteinsChromatinDNA-Binding ProteinsHistone AcetyltransferasesHistonesKAT6A protein, humanKAT6B protein, humanLysineNuclear ProteinsbromodomainBRPF2developmental disorderepigenetic regulatorhistone acetylationintellectual disabilityPHD fingerPWWP domainPZP domain

Identifiers

PMID27939640
PMCPMC5223032
OpenAlexW2560767699

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.