Assessment of MIR200B Polymorphisms Association with Sight-Threatening Diabetic Retinopathy.

Purpose: To assess the possible association between MIR200B variations and sight-threatening diabetic retinopathy (STDR). Methods: A total number of 141 diabetes mellitus patients were enrolled in the study and divided into two groups including 76 patients diagnosed with STDR assigned to the case group, and 65 subjects without STDR considered in the control group. Peripheral blood specimens were used to extract the DNA content, and the primary MIR200B encoding sequence was amplified using a polymerase chain reaction. Then, the amplified DNA was sequenced by the Sanger method. The sequences were compared to the MIR200B reference sequence to find sequence variations. RNAfold, miRVaS, and Mfold bioinformatics web servers were employed to predict the potential effects of the identified variations on RNA structure. Results: Two MIR200B gene variants were identified. Although both variations were found more frequent in cases than controls, statistical analysis of allelic and genotypic features did not reach statistical significance. Conclusions: In silico analysis showed mild changes in MIR200B secondary structure and increased free energy in the presence of one of the identified variants (g.1167183G>A; rs72563729). Increasing the sample size in future studies may help a more accurate interpretation of the allelic association of MIR200B variations with STDR.

PRPH2 mutation as the cause of various clinical manifestations in a family affected with inherited retinal dystrophy.

Background/Objectives: To reveal the underlying genetic defect in a complex family affected with different clinical features of inherited retinal dystrophy, we carried out whole exome sequencing followed by confirmatory molecular tests.Materials and Methods: Complete ophthalmic examinations were performed for available affected family members. Whole exome sequencing, bioinformatics analysis, Sanger sequencing confirmation, and segregation analysis were done to identify the causative mutation.Results: Clinical findings suggested fundus flavimaculatus as an early clinical feature progressing to an extensive chorioretinal atrophy involving the macula and mid-periphery of the fundus in one parent and central areolar chorioretinal dystrophy (CACD) as the most probable clinical diagnosis in another parent. Macular pattern dystrophy for one of their daughters and a Leber congenital amaurosis (LCA) like phenotype for the daughter with an early onset retinal dystrophy (EORD) phenotype was suggested. We found a known pathogenic nonsense variation in the PRPH2 gene (NM_000322: p.Gln239Ter). The parents with end stage fundus flavimaculatus and CACD diagnosis and their daughter with macular pattern dystrophy were heterozygous for the identified variant. The daughter affected with EORD/LCA like retinal dystrophy was homozygous for the same variation.Conclusions: In this family, the same pathogenic variant in PRPH2 gene showed a wide range of clinical features of extensive chorioretinal macular atrophy with flecks as fundus falvimaculatus to CACD and macular pattern dystrophy in the heterozygous inheritance pattern and early onset/LCA like retinal dystrophy in the patient who was homozygous for the causative variant.