Identification of copy number variants associated with BPES-like phenotypes

Hum Genet. 2008 Dec;124(5):489-98. doi: 10.1007/s00439-008-0574-9. Epub 2008 Oct 25.

Abstract

Blepharophimosis-Ptosis-Epicanthus inversus syndrome (BPES) is a well-characterized rare syndrome that includes an eyelid malformation associated with (type I) or without premature ovarian failure (type II). Patients with typical BPES have four major characteristics: blepharophimosis, ptosis, epicanthus inversus and telecanthus. Mutations in the FOXL2 gene, encoding a forkhead transcription factor, are responsible for the majority of both types of BPES. However, many patients with BPES-like features, i.e., having at least two major characteristics of BPES, have an unidentified cause. Here, we report on a group of 27 patients with BPES-like features, but without an identified genetic defect in the FOXL2 gene or flanking region. These patients were analyzed with whole-genome high-density arrays in order to identify copy number variants (CNVs) that might explain the BPES-like phenotype. In nine out of 27 patients (33%) CNVs not previously described as polymorphisms were detected. Four of these patients displayed psychomotor retardation as an additional clinical characteristic. In conclusion, we demonstrate that BPES-like phenotypes are frequently caused by CNVs, and we emphasize the importance of whole-genome copy number screening to identify the underlying genetic causes of these phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blepharophimosis / genetics*
  • Blepharoptosis / genetics*
  • Chromosome Aberrations
  • Eyelids / abnormalities
  • Female
  • Gene Dosage*
  • Genetic Variation
  • Humans
  • In Situ Hybridization, Fluorescence
  • Intellectual Disability / genetics
  • Male
  • Pedigree
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Syndrome