Expanding the phenotypic spectrum in EP300-related Rubinstein-Taybi syndrome

Am J Med Genet A. 2015 May;167A(5):1111-6. doi: 10.1002/ajmg.a.36883. Epub 2015 Feb 25.

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.

Keywords: EP300; Rubinstein-Taybi syndrome; congenital anomalies; whole genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chromosome Mapping
  • E1A-Associated p300 Protein / genetics*
  • Exome / genetics
  • Female
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Mutation*
  • Pregnancy
  • Radiography
  • Rubinstein-Taybi Syndrome / diagnostic imaging
  • Rubinstein-Taybi Syndrome / etiology
  • Rubinstein-Taybi Syndrome / genetics*
  • Rubinstein-Taybi Syndrome / physiopathology
  • Sequence Deletion
  • Spine / diagnostic imaging
  • Spine / physiopathology
  • Urogenital Abnormalities / genetics*
  • Urogenital Abnormalities / physiopathology

Substances

  • E1A-Associated p300 Protein
  • EP300 protein, human