title: First case report of inherited Rubinstein-Taybi syndrome associated with a novel EP300 variant.
abstract: BACKGROUND
  Rubinstein-Taybi syndrome (RSTS; OMIM #180849, #613684) is a rare autosomal dominant genetic condition characterized by broad thumbs and halluces, facial dysmorphism, short stature and variable degree of intellectual disability. RSTS is associated with mutations in CREBBP and EP300 genes in 50-60% and 5-8% of cases, respectively. The majority of cases are de novo heterozygous mutations.
  
  
  METHODS
  Here we describe a familial RSTS case, associated with a novel EP300 mutation. The proband was a 9 years old female, with mild learning difficulties. Her mother, who also had learning difficulties, was found to have short and broad thumbs. MLPA and panel-based NGS of CREBBP and EP300 were performed. A novel heterozygous frameshift mutation in exon 31 of the EP300 gene (c.7222_7223del; p.(Gln2408Glufs*39)) was found in both.
  
  
  CONCLUSIONS
  This case represents the first case of inherited EP300-RSTS. The location of the frameshift deletion not affecting HAT domain and PHD finger, could explain the mild phenotype and the well-preserved intelligence. These patients are mildly affected, and this case highlights the possible missed diagnosis. We would recommend molecular testing of apparently healthy parents, and in the case of inherited mutations, of all adult first degree relatives at risk.
authors.affiliation: Molecular Diagnostics Laboratory, Fundación Rioja Salud, Logroño, La Rioja, Spain.
authors.forename: María
authors.initials: M
authors.lastname: López
authors.affiliation: Clinical Genetics, Department of Pediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Seidel
authors.affiliation: Molecular Diagnostics Laboratory, Fundación Rioja Salud, Logroño, La Rioja, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Santibáñez
authors.affiliation: Molecular Diagnostics Laboratory, Fundación Rioja Salud, Logroño, La Rioja, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cervera-Acedo
authors.affiliation: Section of Neuropaediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Castro-de Castro
authors.affiliation: Molecular Diagnostics Laboratory, Fundación Rioja Salud, Logroño, La Rioja, Spain. edominguez@riojasalud.es.|Center for Biomedical Research (CIBIR), C/Piqueras 98, C.P. 26006, Logroño, Spain. edominguez@riojasalud.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Domínguez-Garrido
mesh_terms: D002648:Child; D050881:E1A-Associated p300 Protein / Q000235:genetics*; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D010641:Phenotype; D012415:Rubinstein-Taybi Syndrome / Q000175:diagnosis / Q000235:genetics*
chemical_list: D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human
keywords: Case report; EP300; Familial-RSTS; Inheritance; RSTS; Rubinstein-Taybi syndrome