Association of TGFBI variants with Congenital and Juvenile onset open angle glaucoma.

Abstract

Purpose: To describe a novel association of TGFBI variants with congenital glaucoma in a family with GAPO (growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy) syndrome as well as among unrelated cases of Juvenile onset open angle glaucoma (JOAG) along with the mechanistic impact of the variants on the protein. Methods: This study of one family of GAPO with congenital glaucoma and three unrelated patients of JOAG analysed a common link to glaucoma pathogenesis. We report ocular features of 3 girls with GAPO syndrome born of consanguineous marriage in a multi- generation consanguineous family. The proband (a 4year old girl) and her younger sibling (1year old girl) were operated for bilateral congenital glaucoma in both eyes. The elder sibling (10year old female) had features of GAPO syndrome without glaucoma. Results: A genetic evaluation using whole exome sequencing revealed a homozygous ANTXR1 mutation in all three affected siblings with GAPO. No other mutations were detected in the genes associated with glaucoma. A rare missense variant in the TGFBI gene was shared in the two siblings with congenital glaucoma and GAPO syndrome. We further found three other unrelated patients with JOAG with no known glaucoma causing gene mutations but having three different missense variants in the TGFBI gene. One of these JOAG patients had familial granular corneal dystrophy. Molecular dynamic simulations of the TGFBI and 3-D structural models of three of its variants showed sig­nificant alterations, which could influence TGFBI function. Conclusions: Variations in the TGFBI gene could have a possible role in the pathogenesis of congenital and Juvenile onset open angle glaucomas that needs further evaluation.

Bilateral Acute Retinal Necrosis From Ocular Syphilis in a Nonimmunocompromised Patient

“…Bacterial and parasitic pathogens, such as Bartonella henselae , Mycobacterium tuberculosis , Toxoplasma species, and Treponema pallidum (the bacterium causing syphilis), may also cause ARN. Noninfectious causes of retinitis include neoplastic retinal lymphoma and autoimmune diseases, for instance, systemic lupus erythematosus and Behçet disease 2 . Because necrotizing retinitis due to syphilis is rare and closely resembles the clinical presentation caused by viral pathogens, syphilitic retinal necrosis (ie, ocular syphilis) poses a diagnostic challenge, especially in patients who are negative for HIV.…”