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


Journal

American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741

Informations de publication

Date de publication:
07 2022
Historique:
revised: 17 11 2021
received: 26 04 2021
accepted: 23 11 2021
pubmed: 11 3 2022
medline: 15 6 2022
entrez: 10 3 2022
Statut: ppublish

Résumé

The Rubinstein-Taybi syndrome (RSTS) is a rare developmental disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, intellectual disability, growth deficiency, and recurrent infections. Mutations in the cyclic adenosine monophosphate response element-binding protein (CREB)-binding protein (CREBBP) or in the E1A-associated protein p300 (EP300) genes have been demonstrated in 55% (RSTS1) and up to 8% of the patients (RSTS2), respectively. Dysfunction of immune response has been reported in a subgroup of individuals with RSTS. Here we characterize two patients carrying the same EP300 variant and distinctive RSTS features (including congenital heart abnormalities, short stature, feeding problems, and gastroesophageal reflux). Whole exome sequencing did not support a dual molecular diagnosis hypothesis. Nonetheless, patients showed distinct clinical manifestations and immunological features. The most severe phenotype was associated with reduced T-cell production and diversity. This latter feature was confirmed in a control group of four RSTS patients.

Identifiants

pubmed: 35266289
doi: 10.1002/ajmg.a.62719
doi:

Substances chimiques

CREB-Binding Protein EC 2.3.1.48
E1A-Associated p300 Protein EC 2.3.1.48
EP300 protein, human EC 2.3.1.48

Types de publication

Case Reports Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2129-2134

Informations de copyright

© 2022 Wiley Periodicals LLC.

Références

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Auteurs

Francesco Saettini (F)

Pediatric Hematology Outpatient Clinic, Pediatric Department, Fondazione MBBM, Monza, Italy.
Centro Ricerca M. Tettamanti, University of Milano Bicocca, Fondazione MBBM/San Gerardo Hospital, Monza, Italy.

Grazia Fazio (G)

Centro Ricerca M. Tettamanti, University of Milano Bicocca, Fondazione MBBM/San Gerardo Hospital, Monza, Italy.

Maria Teresa Bonati (MT)

Ambulatorio di Genetica Medica, Istituto Auxologico Italiano, IRCCS, Milano, Italy.

Daniele Moratto (D)

Flow Cytometry Laboratory, Diagnostic Department, ASST Spedali Civili, Brescia, Italy.

Valentina Massa (V)

Department of Medical Genetics, University of Milan, Milan, Italy.

Elisabetta Di Fede (E)

Department of Medical Genetics, University of Milan, Milan, Italy.

Silvia Castiglioni (S)

Department of Medical Genetics, University of Milan, Milan, Italy.

Daniela Marchetti (D)

Laboratorio di Genetica Medica, ASST-Papa Giovanni XXIII, Bergamo, Italy.

Marco Chiarini (M)

Flow Cytometry Laboratory, Diagnostic Department, ASST Spedali Civili, Brescia, Italy.

Alessandra Sottini (A)

Centro di Ricerca Emato-oncologica AIL (CREA), ASST Spedali Civili, Brescia, Italy.

Maria Iascone (M)

Laboratorio di Genetica Medica, ASST-Papa Giovanni XXIII, Bergamo, Italy.

Giovanni Cazzaniga (G)

Centro Ricerca M. Tettamanti, University of Milano Bicocca, Fondazione MBBM/San Gerardo Hospital, Monza, Italy.

Luisa Imberti (L)

Centro di Ricerca Emato-oncologica AIL (CREA), ASST Spedali Civili, Brescia, Italy.

Andrea Biondi (A)

Pediatric Hematology Outpatient Clinic, Pediatric Department, Fondazione MBBM, Monza, Italy.
Centro Ricerca M. Tettamanti, University of Milano Bicocca, Fondazione MBBM/San Gerardo Hospital, Monza, Italy.

Cristina Gervasini (C)

Department of Medical Genetics, University of Milan, Milan, Italy.

Raffaele Badolato (R)

Pediatrics Clinic and A. Nocivelli Institute for Molecular Medicine A, Department of Clinical and Experimental Sciences, University of Brescia, ASST-Spedali Civili, Brescia, Italy.

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