Association of transforming growth factor beta induced mutations with congenital and juvenile onset open angle glaucoma

Abstract

AbstractPurpose: To investigate the molecular basis of congenital glaucoma in a family with GAPO (growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy) syndrome.Methods: We report ocular features of three girls with GAPO syndrome born of consanguineous marriage in a multi‐ generation consanguineous family. The proband (4 year old girl) and her younger sibling (1 year old girl) were operated for bilateral congenital glaucoma in both eyes. The elder sibling (10 year old female) had features of GAPO syndrome but did not manifest features of glaucoma.Results: A genetic evaluation using whole exome sequencing revealed a homozygous ANTXR1 mutation in all 3 affected siblings with GAPO. No other mutations were detected in the genes associated with glaucoma. A rare missense mutation in Transforming Growth Factor Beta Induced (TGFBI) gene was shared in the two siblings with congenital glaucoma and GAPO syndrome. We then looked for the presence of TGFBI gene mutations in another cohort of 54 unrelated patients with early onset glaucoma (before 25 years of age) in whom Whole exome sequencing was previously done and no known glaucoma mutations were detected. We found three TGFBI mutations present in three unrelated juvenile onset open angle glaucoma (JOAG) patients, one of whom also had an associated corneal granular dystrophy. None of these patients had any other mutations associated with known genes for glaucoma.Conclusions: Mutations in TGFBI gene could have a role in the pathogenesis of congenital and juvenile onset open angle glaucoma.