BRPF1‐associated intellectual disability, ptosis, and facial dysmorphism in a multiplex family
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 unrecog...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-06-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.665 |
| _version_ | 1818947027552174080 |
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| author | Naomi Pode‐Shakked Ortal Barel Ben Pode‐Shakked Aviva Eliyahu Amihood Singer Omri Nayshool Nitzan Kol Annick Raas‐Rothschild Elon Pras Mordechai Shohat |
| author_facet | Naomi Pode‐Shakked Ortal Barel Ben Pode‐Shakked Aviva Eliyahu Amihood Singer Omri Nayshool Nitzan Kol Annick Raas‐Rothschild Elon Pras Mordechai Shohat |
| author_sort | Naomi Pode‐Shakked |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T08:24:23Z |
| format | Article |
| id | doaj.art-b1560623a9ca450d95e163da44e0576c |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-12-20T08:24:23Z |
| publishDate | 2019-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-b1560623a9ca450d95e163da44e0576c2022-12-21T19:46:54ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-06-0176n/an/a10.1002/mgg3.665BRPF1‐associated intellectual disability, ptosis, and facial dysmorphism in a multiplex familyNaomi Pode‐Shakked0Ortal Barel1Ben Pode‐Shakked2Aviva Eliyahu3Amihood Singer4Omri Nayshool5Nitzan Kol6Annick Raas‐Rothschild7Elon Pras8Mordechai Shohat9Department of Pediatrics A Edmond and Lily Safra Children's Hospital, Sheba Medical Center Tel‐Hashomer IsraelThe Genomic Unit, Sheba Cancer Research Center Sheba Medical Center Tel‐Hashomer IsraelThe Dr. Pinchas Borenstein Talpiot Medical Leadership Program Sheba Medical Center Tel‐Hashomer IsraelSackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv IsraelCommunity Genetics Public Health Services, Ministry of Health Jerusalem IsraelThe Genomic Unit, Sheba Cancer Research Center Sheba Medical Center Tel‐Hashomer IsraelThe Genomic Unit, Sheba Cancer Research Center Sheba Medical Center Tel‐Hashomer IsraelSackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv IsraelSackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv IsraelSackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv IsraelAbstract 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.https://doi.org/10.1002/mgg3.665blepharophimosisBRPF1intellectual disabilityptosis |
| spellingShingle | Naomi Pode‐Shakked Ortal Barel Ben Pode‐Shakked Aviva Eliyahu Amihood Singer Omri Nayshool Nitzan Kol Annick Raas‐Rothschild Elon Pras Mordechai Shohat BRPF1‐associated intellectual disability, ptosis, and facial dysmorphism in a multiplex family Molecular Genetics & Genomic Medicine blepharophimosis BRPF1 intellectual disability ptosis |
| title | BRPF1‐associated intellectual disability, ptosis, and facial dysmorphism in a multiplex family |
| title_full | BRPF1‐associated intellectual disability, ptosis, and facial dysmorphism in a multiplex family |
| title_fullStr | BRPF1‐associated intellectual disability, ptosis, and facial dysmorphism in a multiplex family |
| title_full_unstemmed | BRPF1‐associated intellectual disability, ptosis, and facial dysmorphism in a multiplex family |
| title_short | BRPF1‐associated intellectual disability, ptosis, and facial dysmorphism in a multiplex family |
| title_sort | brpf1 associated intellectual disability ptosis and facial dysmorphism in a multiplex family |
| topic | blepharophimosis BRPF1 intellectual disability ptosis |
| url | https://doi.org/10.1002/mgg3.665 |
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