PRPH2 (Peripherin/RDS) mutations associated with different macular dystrophies in a Spanish population: a new mutation.
OBJECTIVE
To assess the occurrence of PRPH2 mutations in patients presenting macular dystrophies and to describe their phenotype-genotype correlation.


METHODS
A total of 32 sporadic cases and 13 individuals from 5 families were studied. The patients presented early onset drusen, suspected pattern dystrophy (including adult-onset foveomacular vitelliform dystrophy [AOFVD]), or any presumed macular dystrophy producing neovascularization or atrophic changes documented before patients reached 50 years of age. In case of atrophy, this could be confined to the macula, which was considered to be central areolar choroidal dystrophy (CACD), or extend to the midperiphery of the retina, which we called diffuse macular dystrophy (DMD). Clinical workup and analysis of PRPH2, EFEMP1, and TIMP3 genes were done.


RESULTS
Four mutations of the PRPH2 gene were found in 3 sporadic cases and 3 families (n = 11). A p.R46X mutation, previously described in CACD, was found in 3 members of a family with AOFVD and in a sporadic case with DMD. A p.L45F mutation, described before in retinitis pigmentosa, was found in a sporadic case of AOFVD. A p.R195L mutation previously described in CACD was found in 2 members of a family with CACD. The latter was found in a family and a sporadic case (from the same village as the family) and all of them presented DMD. A new p.V2091 mutation was found in a patient with AOFVD.


CONCLUSIONS
New phenotypes were found for known mutations. No phenotype variation was observed in the members of the 3 families. A new mutation in PRPH2 gene was found.
Coco
Rosa M
RM
Instituto de Oftalmobiología Aplicada (IOBA), Universidad de Valladolid, Valladolid, Spain. rosa@ioba.med.uva.es
Tellería
Juan J
JJ
Sanabria
M Rosa
MR
Rodríguez-Rúa
Enrique
E
García
M Teresa
MT
D000328:Adult; D000368:Aged; D004247:DNA / Q000235:genetics*; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008268:Macular Degeneration / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D064531:Peripherins; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D055815:Young Adult
D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; D004247:DNA