Association of Pattern Dystrophy With an HTRA1 Single-Nucleotide Polymorphism Jaouni T, Averbukh E, Burstyn-Cohen T, et al. Association of pattern dystrophy with an HTRA1 single-nucleotide polymorphism. Arch Ophthalmol. 2012;130(8): Copyright restrictions may apply

Introduction The genetic basis of most cases of adult-onset foveomacular vitelliform dystrophy (AOFVD) and butterfly-shaped pigment dystrophy (BSPD) forms of pattern dystrophy (PD) is unknown. There are clinical similarities and overlap in phenotypes of PD and age- related macular degeneration (AMD). Objective: To evaluate whether AOFVD and BSPD are associated with risk single-nucleotide polymorphisms (SNPs) for AMD. Copyright restrictions may apply

This was a tertiary referral center–based cross-sectional study. Study included the following: –35 Consecutive patients with BSPD and AOFVD. –317 Patients with AMD. –159 Unaffected individuals. Copyright restrictions may apply Methods

Demographics, clinical information, and ophthalmic imaging studies were collected. Sequencing was performed for the peripherin/RDS and BEST1 genes. Genotyping was performed for SNPs in the genes for complement factor H (CFH) (rs ), HTRA1 (rs ), and complement component 3 (C3) (rs ). Statistical analysis included logistic regression, Fisher exact, and χ 2 tests. Copyright restrictions may apply Methods

AOFVD and BSPD were diagnosed in 24 (68.6%) and 11 (31.4%) of the 35 patients, respectively. In patients with PD, the mean (SD) age was 75.3 (10) years and the median visual acuity was 0.7. The risk allele in HTRA1 was associated with patients with PD compared with unaffected individuals (odds ratio = 1.72; 95% CI, ; P =.03). The HTRA1 SNP showed similar prevalence in patients with AMD and PD. The CFH risk allele was significantly less common in patients with PD compared with patients with AMD (odds ratio = 0.47; 95% CI, ; P =.002). No mutations in peripherin/RDS or BEST1 were detected. There was no correlation between the presence of the AMD risk SNPs and the phenotype or development of choroidal neovascularization. Copyright restrictions may apply Results

Copyright restrictions may apply

Results

Copyright restrictions may apply

PD phenotypes may have variable visual outcomes and age at onset when associated with peripherin/RDS mutations compared with the HTRA1 SNP. PD phenotypes and AMD may have overlapping clinical features as well as similar genetic risk factors in some of the cases (HTRA1 risk SNP). Unlike the HTRA1 SNP, the CFH risk SNP for AMD is not associated with AOFVD. Copyright restrictions may apply Comment

Further research is required to characterize the genetics of PD phenotypes, which are not associated with peripherin/RDS mutations. Underlying genetic factors as well as other modulating factors for the variable phenotypes of PD remained to be identified. Copyright restrictions may apply Comment

If you have questions, please contact the corresponding author: –Itay Chowers, MD, Department of Ophthalmology, Hadassah–Hebrew University Medical Center, POB 12000, Jerusalem, Israel, Funding/Support The study was supported by a grant from the Israel Science Foundation (Dr Chowers) and by the Hadassah Medical Center (Dr Jaouni). Copyright restrictions may apply Contact Information