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

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)‐bindi...

Full description

Saved in:
Bibliographic Details
Published in:American journal of medical genetics. Part A 2022-07, Vol.188 (7), p.2129-2134
Main Authors: Saettini, Francesco, Fazio, Grazia, Bonati, Maria Teresa, Moratto, Daniele, Massa, Valentina, Di Fede, Elisabetta, Castiglioni, Silvia, Marchetti, Daniela, Chiarini, Marco, Sottini, Alessandra, Iascone, Maria, Cazzaniga, Giovanni, Imberti, Luisa, Biondi, Andrea, Gervasini, Cristina, Badolato, Raffaele
Format: Article
Language:English
Subjects:
AMP
CREBBP
Cyclic AMP response element-binding protein
Developmental disabilities
EP300
Gastroesophageal reflux
Immune response
inborn errors of immunity
Intellectual disabilities
Patients
Phenotypes
Rubinstein–Taybi syndrome
syndromic immunodeficiency
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.62719