BRPF1‐associated intellectual disability, ptosis, and facial dysmorphism in a multiplex family. Issue 6 (24th April 2019)

• Record Type: Journal Article
• Authors: Pode‐Shakked, Naomi; Barel, Ortal; Pode‐Shakked, Ben; Eliyahu, Aviva; Singer, Amihood; Nayshool, Omri; Kol, Nitzan; Raas‐Rothschild, Annick; Pras, Elon; Shohat, Mordechai
• Is Part Of: Molecular genetics & genomic medicine. Volume 7:Issue 6(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-04-24
• Subjects: blepharophimosis -- BRPF1 -- intellectual disability -- ptosis; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.665
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: 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. Abstract : A novel heterozygous truncating mutation in BRPF1 causes intellectual disability of variable severity, ptosis/blepharophimosis, and additional dysmorphic features in three male siblings and their mother. This multiply affected family further expands the mutational and phenotypic spectrum of the newly recognized BRPF1‐associated neurodevelopmental disorder