Identical <scp><i>EP300</i></scp> variant leading to Rubinstein–Taybi syndrome with different clinical and immunologic phenotype

Saettini, Francesco; Fazio, Grazia; Bonati, Maria Teresa; Moratto, Daniele; Massa, Valentina; Fede, Elisabetta Di; Castiglioni, Silvia; Marchetti, Daniela; Chiarini, Marco; Sottini, Alessandra; Iascone, Maria; Cazzaniga, Giovanni; Biondi, Andrea; Gervasini, Cristina; Badolato, Raffaele

doi:10.1002/ajmg.a.62719

Cited by 3 publications

(1 citation statement)

References 10 publications

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“…Neurogenesis; NCC differentiation to craniofacial elements Rubinstein-Taybi syndrome (Babu et al, 2018;Bartsch et al, 2010;Bhattacherjee et al, 2009;Hamilton et al, 2016;Saettini et al, 2022;Warner et al, 2002Warner et al, , 2006)…”

Section: Chd7mentioning

confidence: 99%

Epigenetic regulation of craniofacial development and disease

Shull,

Artinger

2023

Birth Defects Research

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BackgroundThe formation of the craniofacial complex relies on proper neural crest development. The gene regulatory networks (GRNs) and signaling pathways orchestrating this process have been extensively studied. These GRNs and signaling cascades are tightly regulated as alterations to any stage of neural crest development can lead to common congenital birth defects, including multiple syndromes affecting facial morphology as well as nonsyndromic facial defects, such as cleft lip with or without cleft palate. Epigenetic factors add a hierarchy to the regulation of transcriptional networks and influence the spatiotemporal activation or repression of specific gene regulatory cascades; however less is known about their exact mechanisms in controlling precise gene regulation.AimsIn this review, we discuss the role of epigenetic factors during neural crest development, specifically during craniofacial development and how compromised activities of these regulators contribute to congenital defects that affect the craniofacial complex.

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Section: Chd7mentioning

confidence: 99%

Epigenetic regulation of craniofacial development and disease

Shull,

Artinger

2023

Birth Defects Research

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Expanding the clinical spectrum of PPP3CA variants - alternative isoforms matter

Castiglioni,

Pezzoli,

Pezzani

et al. 2024

Orphanet J Rare Dis

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Background the protein phosphatase 3 catalytic subunit alpha (PPP3CA) gene encodes for the alpha isoform of the calcineurin catalytic subunit, which controls the phosphorylation status of many targets. Currently, 23 pathogenic variants of PPP3CA are known, with clinical manifestations varying by mutation type and domain. Results through whole exome sequencing, we found two de novo variants in PPP3CA: a frameshift variant predicted leading to a truncated protein in Pt.1 and a splicing variant in Pt.2 associated with mild phenotype. PPP3CA is ubiquitously expressed with tissue-specificity of; namely, splicing isoform 1 prevailing over isoform 2 in the central nervous system. By analyzing isoform distribution in patient-derived cell lines, we highlight a skewed expression of both isoforms in Pt.1, whereas only isoform 2 shows a moderate reduction in Pt.2. In contrast, we did not observe significant abundance changes at the protein level. Cell lines derived from Pt.1 showed a reduced proliferation, associated with an increase in cell death and the upregulation of the unfolded protein response (UPR) pathway. Conclusion data suggest that an aberrant PPP3CA protein in Pt.1 could lead to UPR activation resulting in increased cell death. In Pt.2 an imbalance between the two main isoforms possibly explains the peculiar pathological manifestations, such as a moderate developmental delay.

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Sindromi, genetica e immunologia: dall’inizio della fine alla fine dell’inizio

Guerra,

Saettini,

Biondi

2023

Medico E Bambino

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Syndromic immunodeficiencies are defined as a group of immunodeficiencies in which the immunological defect may be found only in a subgroup of patients. They fall within a more complex clinical picture and may not represent the primary clinical problem (i.e. DiGeorge syndrome, ataxia-telangiectasia, CHARGE syndrome, Kabuki syndrome etc.). Along with well-known and recognized syndromic immunodeficiencies, immunological abnormalities have been recently described in genetic syndromes that were not previously considered as inborn errors of immunity. The paper describes the cases of two patients affected by two rare genetic syndromes, namely Jacobsen syndrome and Rubinstein-Taybi syndrome. In the first case, the immunological phenotype of Jacobsen syndrome has been expanded. In the second, the growing body of evidence has pointed out that patients with Rubinstein-Taybi syndrome may present with immunological abnormalities.

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Identical EP300 variant leading to Rubinstein–Taybi syndrome with different clinical and immunologic phenotype

Cited by 3 publications

References 10 publications

Epigenetic regulation of craniofacial development and disease

Epigenetic regulation of craniofacial development and disease

Expanding the clinical spectrum of PPP3CA variants - alternative isoforms matter

Sindromi, genetica e immunologia: dall’inizio della fine alla fine dell’inizio

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