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Abstract #117855 Published in IGR 24-4
Distribution of variants in patients with early onset glaucoma
Gupta V; Panigrahi A; Panigrahi A; Somarajan BI; Gupta S; Tripathy K; Singh A; Tandon R; Pradhan D; Sharma A; Kushwaha T; Inampudi KKMolecular Vision 2023; 29: 365-377
PURPOSE: To describe a novel association of variants with congenital glaucoma in a family with GAPO (growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy) syndrome, as well as among other unrelated cases of juvenile onset open-angle glaucoma (JOAG) and primary congenital glaucoma (PCG). METHODS: This study of one family of GAPO with congenital glaucoma and three unrelated patients with JOAG analyzed a common link to glaucoma pathogenesis. Three girls with GAPO syndrome born to consanguineous parents in a multi-generation consanguineous family were identified. Two of the girls had congenital glaucoma in both eyes, while the elder sibling (a 10-year-old female) had features of GAPO syndrome without glaucoma. RESULTS: A genetic evaluation using whole exome sequencing revealed a novel homozygous 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 gene was shared in the two siblings with congenital glaucoma and GAPO syndrome. We found three other unrelated patients with JOAG and one patient with primary congenital glaucoma with no known glaucoma causing gene mutations, but having four different missense variants in the gene. One of these patients with JOAG had familial granular corneal dystrophy. Molecular dynamic simulations of TGFBI and 3-D structural models of three of its variants showed significant alterations that could influence TGFBI protein function. CONCLUSIONS: The possibility that variations in the gene could have a possible role in the pathogenesis of congenital and juvenile onset open-angle glaucomas needs further evaluation.
Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi.
