RESUMO
BACKGROUND: The peripherin-2 (PRPH2) gene encodes a photoreceptor-specific transmembrane-protein called peripherin-2 which is critical for the formation and maintenance of rod and cone outer segments. Over 90 different disease-causing mutations in PRPH2 have been identified which cause a variety of forms of macular degeneration and also retinopathia pigmentosa. PATIENTS/MATERIAL AND METHODS: This study is a retrospective observational study of 3 patients ascertained over a 5 month period in the ophthalmogenetic consultation of the university ophthalmic clinic. So far, the patients were followed for 8 months at least. Data examined included clinical history, pedigree analysis, ophthalmological examination, fundus photography, autofluorescence imaging, optical coherence tomography, Arden colour test, Goldmann perimetry and detailed electrophysiological assessment. Blood samples were taken for DNA extraction and mutation analysis of PRPH2 and ABCA4, BEST1, C1QTNF5, CDH3, CNGB3, ELOVL4, FSCN2, PROM1, RDH12, RP1L1, RPGR, TIMP3 was performed. RESULTS: All patients had presented with clinically evident maculopathy and visual acuities in the range of 1/50 Metervisus to 0.8 p [dec.]. All had specific electroretinogrammes. All PRPH2 mutations were autosomal dominant. One family was heterozygous for a previously reported missense mutation in the PRPH2 gene c.514C>T, p.R172W. The other patient was heterozygous for a so far non-described PRPH2 deletion and frameshift mutation c.74_77delGGTT, p.W25SfsX12 leading most likely to a truncated, dysfunctional protein. All patients showed a significant, inter-individual phenotypical variability. CONCLUSION: The data add to the documented phenotypical variability of PRPH2 mutations and describe the c.74_77delGGTT, p.W25SfsX12 mutation within PRPH2 for the first time. FAF, OCT and electrophysiological exams are helpful tools for diagnosis and evaluation of macular disease due to PRPH2 mutations.