<scp><i>BRPF1</i></scp>‐associated syndrome: A patient with congenital ptosis, neurological findings, and normal intellectual development

Souza, Josiane; Valle, Daniel Almeida do; Santos, Mara Lucia Schmidt Ferreira; Colomé, Fernanda Bonilla; Teive, Hélio Afonso Ghizoni; Freitas, Renato da Silva; Herai, Roberto Hirochi

doi:10.1002/ajmg.a.62706

Cited by 7 publications

(10 citation statements)

References 13 publications

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“…T A B L E 1 The clinical features of reported IDDDFP cases. have been reported so far (Demeulenaere et al, 2019;Keywan et al, 2020;Mattioli et al, 2017;Pode-Shakked et al, 2019;Souza et al, 2022;Yan et al, 2017Yan et al, , 2020. Our patients have no visual abnormalities but have ocular features such as ptosis (all patients), blepharophimosis (patient 1), and hypertelorism (all patients).…”

Section: Discussionmentioning

confidence: 55%

“…Additionally, other ocular and visual abnormalities were seen in the majority of the patients (28/36). Patients with hypermetropia, blepharophimosis, downslanting palpebral fissures, strabismus, monocular esotropia, latent nystagmus, strabismus, and bilateral iris coloboma have been reported so far (Demeulenaere et al, 2019; Keywan et al, 2020; Mattioli et al, 2017; Pode‐Shakked et al, 2019; Souza et al, 2022; Yan et al, 2017, 2020). Our patients have no visual abnormalities but have ocular features such as ptosis (all patients), blepharophimosis (patient 1), and hypertelorism (all patients).…”

Section: Discussionmentioning

confidence: 99%

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Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Çanakkale with intellectual disability and dysmorphic facies: Case report and review of the literature

Kose,

Kaya,

Akcan

et al. 2023

American J of Med Genetics Pt A

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Intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP) (MIM#617333) is an autosomal dominant disorder characterized by delayed psychomotor development, intellectual disability (ID), and dysmorphic facial features due to pathogenic variations in the Bromodomain-and PHD Finger-Containing Protein (BRPF1) (MIM#602410) gene. Herein, we report the first Turkish patients with IDDDFP. Additionally, the patients had hematopoietic disorders such as anemia and thrombocytopenia, which have not been previously described in IDDDFP patients.Genetic testing using Whole Exome Sequencing (WES) revealed a novel heterozygous c.1433G > A; p.W478* (NM_004634.3) pathogenic variant on exon 3 of the BRPF1 gene. The patients demonstrated classical features of IDDDFP such as intellectual disability, developmental delay, ptosis, micro and retrognathia, and dysmorphic facial features, in addition to the anemia and thrombocytopenia. Apart from the variant in BRPF1, no additional genomic changes were detected by WES and chromosomal microarray analysis (CMA). Hopefully, our novel report on the hematopoietic anomalies of our patients due to BRPF1 will expand upon the clinical spectrum of IDDDFP, encourage further studies about BRPF1-hematopoietic system relations, and affect the diagnostic and therapeutic schemes of hematopoietic system disorders.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Çanakkale with intellectual disability and dysmorphic facies: Case report and review of the literature

Kose,

Kaya,

Akcan

et al. 2023

American J of Med Genetics Pt A

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“…Common clinical features of IDDDFP include intellectual disability (ID), global developmental delay, hypotonia, facial dysmorphisms, ptosis, and/or blepharophimosis. Less frequently reported clinical features include hand and foot anomalies, brain anomalies, microcephaly, behavioral anomalies, growth retardation, and seizures [1][2][3][4][5][6][7][8][9]. Maternal mosaicism has been previously reported in Yan et al [2].…”

Section: Discussionmentioning

confidence: 93%

Mosaicism in BRPF1-Related Neurodevelopmental Disorder: Report of Two Sisters and Literature Review

Bayanbold,

Younger,

Darbro

et al. 2023

Case Reports in Genetics

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Bromodomain and PHD finger containing 1 (BRPF1)-related neurodevelopmental disorder is characterized by intellectual disability, developmental delay, hypotonia, dysmorphic facial features, ptosis, and blepharophimosis. Both de novo and inherited pathogenic variants have been previously reported in association with this disorder. We report two affected female siblings with a novel variant in BRPF1 c.2420_2433del (p.Q807Lfs ∗ 27) identified through whole-exome sequencing. Their history of mild intellectual disability, speech delay, attention deficient hyperactivity disorder (ADHD), and ptosis align with the features previously reported in the literature. The absence of the BRPF1 variant in parental buccal samples provides evidence of a de novo frameshift pathogenic variant, most likely as a result of parental gonadal mosaicism, which has not been previously reported. The frameshift pathogenic variant reported here lends further support to haploinsufficiency as the underlying mechanism of disease. We review the literature, compare the clinical features seen in our patients with others reported, and explore the possibility of genotype-phenotype correlation based on the location of pathogenic variants in BRPF1. Our study helps to summarize available knowledge and report the first case of a de novo frameshift pathogenic variant in BRPF1 in two siblings with this neurodevelopmental disorder.

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“…Thus, an interesting question is whether BRPF1 mutations in humans cause developmental abnormalities. To date, 43 cases of BRPF1 mutations reported confirm that BRPF1 is a causal gene for intellectual disability (ID) in a disease known as intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP) (12 cases [ 13 ], 10 cases [ 106 ], 12 cases [ 107 ], 1 case [ 108 ], 1 case [ 109 ], 1 case [ 110 ], 4 cases [ 111 ], 1 case [ 112 ], 1 case with schizophrenia and mild ID [ 113 ]). The sites of BRPF1 mutations involved in IDDDFP are summarized in Figure 2 .…”

Section: Human Diseases With Mutations In the Brpf1-kat6a/kat6b Complexmentioning

confidence: 99%

“…4 other de novo truncating variants (BRPF1-p.Gln629Hisfs*34, p.Val707Argfs*8, p.Arg833*, and p.Met973Asnfs*24) have also been identified in 4293 UK individuals in the Deciphering Developmental Disorders (DDD) study [ 114 ]. Additional BRPF1 variants reported include a de novo LoF variant (p.Ala396LeufsTer69) in a child of sudden unexplained death [ 112 ], a truncating variant (p.Q186*) in three affected siblings and their mother [ 111 ], a variant (p.Val352Leu) in a girl [ 110 ], a de novo nonsense variant (p.Glu219*) in a boy [ 109 ] and a rare nonsense variant (p.Gln322*) in a patient with normal intellectual development [ 108 ]. A BRPF1 Tyr406His variant was identified in an autistic individual, but the pathogenicity remains elusive [ 115 ].…”

Section: Human Diseases With Mutations In the Brpf1-kat6a/kat6b Complexmentioning

confidence: 99%

BRPF1-KAT6A/KAT6B Complex: Molecular Structure, Biological Function and Human Disease

Liu

Cao

et al. 2022

Cancers

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The bromodomain and PHD finger–containing protein1 (BRPF1) is a member of family IV of the bromodomain-containing proteins that participate in the post-translational modification of histones. It functions in the form of a tetrameric complex with a monocytic leukemia zinc finger protein (MOZ or KAT6A), MOZ-related factor (MORF or KAT6B) or HAT bound to ORC1 (HBO1 or KAT7) and two small non-catalytic proteins, the inhibitor of growth 5 (ING5) or the paralog ING4 and MYST/Esa1-associated factor 6 (MEAF6). Mounting studies have demonstrated that all the four core subunits play crucial roles in different biological processes across diverse species, such as embryonic development, forebrain development, skeletal patterning and hematopoiesis. BRPF1, KAT6A and KAT6B mutations were identified as the cause of neurodevelopmental disorders, leukemia, medulloblastoma and other types of cancer, with germline mutations associated with neurodevelopmental disorders displaying intellectual disability, and somatic variants associated with leukemia, medulloblastoma and other cancers. In this paper, we depict the molecular structures and biological functions of the BRPF1-KAT6A/KAT6B complex, summarize the variants of the complex related to neurodevelopmental disorders and cancers and discuss future research directions and therapeutic potentials.

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BRPF1‐associated syndrome: A patient with congenital ptosis, neurological findings, and normal intellectual development

Cited by 7 publications

References 13 publications

Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Çanakkale with intellectual disability and dysmorphic facies: Case report and review of the literature

Anemia and thrombocytopenia due to a novel BRPF1 variant in a family from Çanakkale with intellectual disability and dysmorphic facies: Case report and review of the literature

Mosaicism in BRPF1-Related Neurodevelopmental Disorder: Report of Two Sisters and Literature Review

BRPF1-KAT6A/KAT6B Complex: Molecular Structure, Biological Function and Human Disease

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