Invest Ophthalmol Vis Sci. 2014 Jul 31. pii: IOVS-14-14359. doi: 10.1167/iovs.14-14359. [Epub ahead of print]
Molecular Diagnostic Testing by eyeGENE®. Analysis of patients with hereditary retinal dystrophy phenotype involving central vision loss.
Alapati AN1, Goetz K2, Suk J1, Navani M3, Al-Tarouti A4, Jayasundera KT5, Lee P1, Tumminia SJ6, Ayyagari R7.
Purpose: To analyze the genetic test results of probands referred to eyeGENE® with a diagnosis of hereditary maculopathy. Methods: Patients with best macular dystrophy (BMD), doyne honey comb retinal dystrophy (DHRD), sorsby fundus dystrophy (SFD), or late-onset retinal degeneration (LORD) were screened for mutations in BEST1, EFEMP1, TIMP3, and CTRP5, respectively. Patients with pattern dystrophy (PD) were screened for mutations in PRPH2, BEST1, ELOVL4, CTRP5 and ABCA4; patients with cone-rod dystrophy (CRD) were screened for mutations in CRX, ABCA4, PRPH2, ELOVL4 and the c.2513G>A, p.Arg838His variant in GUCY2D. Mutation analysis was performed by dideoxy sequencing. Impact of novel variants was evaluated using the computational tool, PolyPhen. Results: Among the 213 unrelated patients, 38 had BMD, 26 DHRD, 74 PD, 8 SFD, 6 LORD, 54 CRD, 6 with both PD and BMD, and one with no specific clinical diagnosis. BEST1 variants were identified in 25 BMD patients, five with novel variants of unknown significance (VUS). Among the five patients, one was diagnosed with both BMD and PD. Another novel EFEMP1 variant was identified in one DHRD patient. TIMP3 novel variants were found in two SFD patients; PRPH2 variants in 14 PD patients; ABCA4 variants in 4 PD patients; and p.Arg838His GUCY2D mutation in 6 patients diagnosed with dominant CRD, one patient additionally had a CRX VUS. ABCA4 mutations were identified in 15 patients with recessive CRD. Conclusion: Of the 213 samples, 55 patients (26%) had known causative mutations and 13 (6%) patients had a VUS that is possibly pathogenic.
Copyright © 2014 by Association for Research in Vision and Ophthalmology.
- [PubMed - as supplied by publisher]