Genome-wide sequencing expands the phenotypic spectrum of EP300 variants

Gregory Costain; Peter Kannu; Sarah Bowdin

doi:10.1016/j.ejmg.2017.11.002

Genome-wide sequencing expands the phenotypic spectrum of EP300 variants

Eur J Med Genet. 2018 Mar;61(3):125-129. doi: 10.1016/j.ejmg.2017.11.002. Epub 2017 Nov 10.

Authors

Gregory Costain¹, Peter Kannu², Sarah Bowdin³

Affiliations

¹ Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada; Medical Genetics Residency Training Program, University of Toronto, Toronto, ON, M5G 1X8, Canada.
² Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, M5S 1A8, Canada.
³ Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada. Electronic address: sarah.bowdin@addenbrookes.nhs.uk.

PMID: 29133209
DOI: 10.1016/j.ejmg.2017.11.002

Abstract

Many disease genes are defined by their role in causing specific clinically recognizable syndromes. Heterozygous loss of function of the gene EP300 is responsible for a minority of cases of Rubinstein-Taybi syndrome (RSTS). With the application of whole-exome sequencing and whole-genome sequencing, there is the potential to discover new genotype-phenotype correlations. The purpose of this case series is to describe three unrelated females without classic manifestations of RSTS who were unexpectedly found on genome-wide sequencing to have likely pathogenic variants in EP300. These individuals expand our knowledge of the disease spectrum by virtue of their very rare or novel clinical features. Results are placed within the context of all prior published EP300 cases not ascertained by targeted testing, which are disproportionately female compared with a cohort identified because of a clinical suspicion of RSTS (p = 0.01). There are implications for diagnosis, management, and genetic counselling of individuals with EP300-related disease.

Keywords: Choanal atresia; EP300; Hyperinsulinism; Lipomyelomeningocele; Rubinstein-Taybi syndrome; Tumour screening; Whole-exome sequencing; Whole-genome sequencing.

Publication types

Case Reports

MeSH terms

Adult
Child
Child, Preschool
Chromosome Mapping
E1A-Associated p300 Protein / genetics*
Female
Genetic Association Studies
Genome, Human*
Genome-Wide Association Study*
Humans
Infant
Male
Mutation*
Phenotype
Rubinstein-Taybi Syndrome / genetics*
Rubinstein-Taybi Syndrome / pathology
Sequence Analysis, DNA

Substances

E1A-Associated p300 Protein
EP300 protein, human