Combination of retinitis pigmentosa and hearing loss caused by a novel mutation in PRPH2 and a known mutation in GJB2: importance for differential diagnosis of Usher syndrome

Vision Res. 2012 Dec 15:75:71-6. doi: 10.1016/j.visres.2012.07.011. Epub 2012 Jul 25.

Abstract

Purpose of this study was to molecularly characterize a family in which two brothers (46 and 36 years) presented with a combination of retinitis pigmentosa (RP) and severe sensorineural hearing loss while father and sister (71 and 41 years) presented with isolated RP. Retinal phenotype was compared with phenotype of 17 patients with Usher syndrome type 1. Ophthalmological examination included assessment of Snellen visual acuity, color vision with Ishihara tables, Goldmann perimetry (targets II/1-4) and microperimetry. Fundus autofluorescence imaging and optical coherence tomography were performed. Direct sequencing of all coding exons and flanking intronic sequences of GJB2 (gap junction protein, beta 2) and PRPH2 (peripherin 2) genes was performed in younger brother. Other family members were analyzed with sequencing (GJB2), high resolution melt analysis (GJB2) or restriction enzymes (PRPH2). Brothers with hearing loss were found to carry a homozygous c.35 delG mutation in GJB2, the most common mutation associated with recessive hearing loss. All patients were found to carry a novel heterozygous mutation c.389T>C (p.Leu130Pro) on PRPH2. Age of onset was higher in PRPH2 than USH1 patients, however with some overlap. Differentiation from retinal phenotype of USH1 could only be made in the oldest patient, who retained good central visual function after more than three decades of disease.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Connexin 26
  • Connexins / genetics*
  • Diagnosis, Differential
  • Hearing Loss / genetics*
  • Humans
  • Intermediate Filament Proteins / genetics*
  • Male
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Mutation*
  • Nerve Tissue Proteins / genetics*
  • Pedigree
  • Peripherins
  • Retinitis Pigmentosa / genetics*
  • Usher Syndromes / diagnosis
  • Usher Syndromes / genetics*

Substances

  • Connexins
  • GJB2 protein, human
  • Intermediate Filament Proteins
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • PRPH protein, human
  • PRPH2 protein, human
  • Peripherins
  • Connexin 26