BRPF1-associated intellectual disability, ptosis, and facial dysmorphism in a multiplex family.
Adaptor Proteins, Signal Transducing
/ genetics
Adult
Blepharophimosis
/ genetics
Blepharoptosis
/ genetics
DNA-Binding Proteins
/ genetics
Exome
Family
Female
Humans
Intellectual Disability
/ genetics
Male
Muscle Hypotonia
/ genetics
Musculoskeletal Abnormalities
/ genetics
Mutation
Nuclear Proteins
/ genetics
Pedigree
Exome Sequencing
BRPF1
blepharophimosis
intellectual disability
ptosis
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
15
11
2018
revised:
18
02
2019
accepted:
08
03
2019
pubmed:
26
4
2019
medline:
24
6
2020
entrez:
26
4
2019
Statut:
ppublish
Résumé
Over 500 epigenetic regulators have been identified throughout the human genome. Of these, approximately 30 chromatin modifiers have been implicated thus far in human disease. Recently, variants in BRPF1, encoding a chromatin reader, have been associated with a previously unrecognized autosomal dominant syndrome manifesting with intellectual disability (ID), hypotonia, dysmorphic facial features, ptosis, and/or blepharophimosis in 22 individuals. We report a multiply affected nonconsanguineous family of mixed Jewish descent who presented due to ID in three male siblings. Molecular analysis of the family was pursued using whole exome sequencing (WES) and subsequent Sanger sequencing. Whole exome sequencing analysis brought to the identification of a novel heterozygous truncating mutation (c.556C>T, p.Q186*) in the BRPF1 gene in the affected siblings and their mother. The four affected individuals showed varying degrees of intellectual disability, distinct facial features including downslanted palpebral fissures, ptosis, and/or blepharophimosis. Their clinical characteristics are discussed in the context of previously reported patients with the BRPF1-related phenotype. The reported family contributes to the current knowledge regarding this unique and newly recognized genetic disorder, and further implicates the role of BRPF1 in human brain development.
Sections du résumé
BACKGROUND
Over 500 epigenetic regulators have been identified throughout the human genome. Of these, approximately 30 chromatin modifiers have been implicated thus far in human disease. Recently, variants in BRPF1, encoding a chromatin reader, have been associated with a previously unrecognized autosomal dominant syndrome manifesting with intellectual disability (ID), hypotonia, dysmorphic facial features, ptosis, and/or blepharophimosis in 22 individuals.
PATIENTS AND METHODS
We report a multiply affected nonconsanguineous family of mixed Jewish descent who presented due to ID in three male siblings. Molecular analysis of the family was pursued using whole exome sequencing (WES) and subsequent Sanger sequencing.
RESULTS
Whole exome sequencing analysis brought to the identification of a novel heterozygous truncating mutation (c.556C>T, p.Q186*) in the BRPF1 gene in the affected siblings and their mother. The four affected individuals showed varying degrees of intellectual disability, distinct facial features including downslanted palpebral fissures, ptosis, and/or blepharophimosis. Their clinical characteristics are discussed in the context of previously reported patients with the BRPF1-related phenotype.
CONCLUSION
The reported family contributes to the current knowledge regarding this unique and newly recognized genetic disorder, and further implicates the role of BRPF1 in human brain development.
Identifiants
pubmed: 31020800
doi: 10.1002/mgg3.665
pmc: PMC6565580
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
BRPF1 protein, human
0
DNA-Binding Proteins
0
Nuclear Proteins
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e665Informations de copyright
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
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