Genetic testing in four Indian families with suspected Stickler syndrome

Purpose:Stickler syndrome is associated with the development of rhegmatogenous retinal detachment (RRD), and often presents with ocular, auditory, skeletal, and orofacial abnormalities. Molecular analysis has proven effective in diagnosis, confirmation and classification of the disease. We aimed to describe the utility of next-generation sequencing (NGS) in genetic analysis of four Indian families with suspected Stickler syndrome.Methods: The index cases presented with retinal detachment with family history. Genetic analysis in the index case was performed by next-generation sequencing of inherited retinal degeneration genes, and validated by Sanger sequencing followed by co-segregation analysis in the other family members.Results: Twenty patients were included for the genetic analysis (15 males and 5 females from four families). Clinical details were available for 15 patients (30 eyes). Fourteen eyes (11 patients) developed RRD. In the 16 eyes without RRD, 8 underwent barrage laser to lattice degeneration and 8 were under observation. Disease segregating heterozygous mutations with pathogenic/likely pathogenic effect was identified in COL2A1 (c.4318-1G>A, c.141G>A, c.1221+1G>A for 3 families) and COL11A1 (c.1737+1 G>A for 1 family) gene. In addition to the mutation in the COL2A1 gene, a pathogenic heterozygous variant associated with risk for arrhythmogenic right ventricular cardiomyopathy (ARVC) was identified in one member.Conclusion: NGS testing confirmed the presence of the causative gene for Stickler syndrome in the index case followed by evaluation of family members and confirmation of genetic and ocular findings. We believe that this may be the first such report of families with RRD from India.     

Lacrimal gland CD5-positive,primary, extra-nodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT) – Type

Mucosa-associated lymphoid tissue (MALT) lymphoma of the ocular adnexae is rare. A 39-year-old woman presenting with proptosis was diagnosed to have non-Hodgkin’s lymphoma with intermediate-sized cells and lymphoepithelial lesion. Unlike most MALT lymphomas, this lymphoma was found to be CD5-positive. Small lymphocytic lymphoma/chronic lymphocytic leukemia and lymphoplasmacytic lymphoma are two other entities that are CD5-positive and have a morphological pattern similar to MALT lymphoma. The case report and approach to the diagnosis is discussed.     

Arachidonic acid metabolites and peroxide-induced inhibition of [3H]D-aspartate release from bovine isolated retinae

We have previously shown that hydrogen peroxide (H2O2) can inhibit K+-depolarization-evoked [3H]D-aspartate release from bovine isolated retinae. In the present study, we investigated the role of arachidonic acid metabolites in the inhibitory response elicited by H2O2 in the bovine retinae. Furthermore, we examined the direct effect of H2O2 on the production of prostaglandins and isoprostanes in this tissue. Isolated bovine retinae were prepared for studies of [3H]D-aspartate release using the Superfusion Method. Release of [3H]D-aspartate was elicited by Krebs solution containing an iso-osmotic concentration of KCl (50 mM). A direct action of H2O2 on prostaglandin E2 (PGE2) and 8-isoprostane F2alpha (8-iso-PGF2alpha) was also measured by enzyme-linked immunosorbant assay (ELISA). The cyclooxygenase inhibitor, flurbiprofen (3 microM), or the thromboxane-receptor antagonist, SQ 29548 (10 microM) had no significant (p > 0.05) effect on K+-evoked [3H]D-aspartate release. On the other hand, both flurbiprofen (3 microM) and SQ 29548 (10 microM) blocked the inhibition of K+-evoked [3H]D-aspartate induced by H2O2 (30 microM). In concentrations up to 100 microM, H2O2 caused an increase in PGE2 and 8-iso-PGF2alpha over basal levels. For instance, H2O2 (100 microM) increased PGE2 and 8-iso-PGF2alpha over basal levels by 348 +/- 41% and 185 +/- 26 (n = 4), respectively. We conclude that the peroxide-mediated inhibition of [3H]D-aspartate may involve the production of prostaglandins and isoprostanes in the bovine isolated retinae.