title: Expanding the phenotypic spectrum in EP300-related Rubinstein-Taybi syndrome.
abstract: Rubinstein-Taybi syndrome (RSTS) can be caused by heterozygous mutations or deletions involving CREBBP or, less commonly, EP300. To date, only 15 patients with EP300 mutations have been clinically described. Frequently reported manifestations in these patients include characteristic facial and limb features, varying degrees of neurocognitive dysfunction, and maternal preeclampsia. Other congenital anomalies are less frequently reported. We describe a child found to have a de novo EP300 mutation (c.4933C>T, predicted to result in p.Arg1645X) through research-based whole-genome sequencing of the family trio. The child's presentation involved dysmorphic features as well as unilateral renal agenesis, a myelomeningocele, and minor genitourinary anomalies. The involvement of congenital anomalies in all 16 clinically described patients with EP300 mutations (25% of which have been identified by "hypothesis free" methods, including microarray, exome, and whole-genome sequencing) is reviewed. In summary, genitourinary anomalies have been identified in 38%, cardiovascular anomalies in 25%, spinal/vertebral anomalies in 19%, other skeletal anomalies in 19%, brain anomalies in 13%, and renal anomalies in 6%. Our patient expands the phenotypic spectrum in EP300-related RSTS; this case demonstrates the evolving practice of clinical genomics related to increasing availability of genomic sequencing methods.
authors.affiliation: Inova Translational Medicine Institute, Inova Health System, Falls Church, Virginia; Department of Pediatrics, Inova Health System, Falls Church, Virginia; Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Solomon
authors.forename: Dale L
authors.initials: DL
authors.lastname: Bodian
authors.forename: Alina
authors.initials: A
authors.lastname: Khromykh
authors.forename: Gabriela Gomez
authors.initials: GG
authors.lastname: Mora
authors.forename: Brendan C
authors.initials: BC
authors.lastname: Lanpher
authors.forename: Ramaswamy K
authors.initials: RK
authors.lastname: Iyer
authors.forename: Rajiv
authors.initials: R
authors.lastname: Baveja
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Vockley
authors.forename: John E
authors.initials: JE
authors.lastname: Niederhuber
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D050881:E1A-Associated p300 Protein / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D009154:Mutation; D011247:Pregnancy; D011859:Radiography; D012415:Rubinstein-Taybi Syndrome / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D017384:Sequence Deletion; D013131:Spine / Q000000981:diagnostic imaging / Q000503:physiopathology; D014564:Urogenital Abnormalities / Q000235:genetics* / Q000503:physiopathology
chemical_list: D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human
keywords: EP300; Rubinstein-Taybi syndrome; congenital anomalies; whole genome sequencing