Five Novel Mutations in the Rds/Peripherin Gene in Patients With Autosomal Dominant Macular Dystrophy

Abstract

Purpose: : To report the phenotype and genotype associated with autosomal dominant maculopathy caused by mutations in Rds/peripherin gene in a single institution.

Methods: : Between January 2002 and December 2007, a total of 80 DNA samples from probands diagnosed with autosomal dominant macular dystrophy were sequenced using bidirectional sequencing of the 3 exons including the splice donor and acceptor sites. The results of clinical evaluation, electrophysiology (ERG) and imaging were reviewed.

Results: : Twenty six affected probands were found to carry mutations in the Rds/peripherin gene; 11 mutations were identified; 5 of which were novel. 38% of probands had the common p.Arg172 Trp allele. Mean patients age at time of first symptoms and at diagnosis was 37.4+/- 3.3 and 49.2 +/- 1.9 years old [SEM] respectively. Mean Logmar visual acuity at presentation was 0.62+/- 0.11 [SEM]. Forty two percent of patients presented with bull eye maculopathy, 23.1% with pattern dystrophy, 19.2 % maculopathy associated with flecks and 11.5 % with adult vitellifom dystrophy. Sixty five percent of the patient cohort had undergone electrophysiology; the majority of patients had an abnormal pattern ERG P50 component but normal full field ERG. Two patients with nonsense mutations had evidence of full field ERG abnormalities at diagnosis and progressed to extensive retinal disease.

Conclusions: : Mutations in the Rds/peripherin gene result in a wide variety of macular phenotypes and generally there is a good visual prognosis with slow disease progression. Null mutations are more likely to be associated with progression to severe generalised retinal dysfunction.

Keywords: mutations • gene screening • macula/fovea