title: Clinical and genetic aspects of the TGFBI-associated corneal dystrophies.
abstract: Corneal dystrophies are a group of inherited disorders localized to various layers of the cornea that affect corneal transparency and visual acuity. The deposition of insoluble protein materials in the form of extracellular deposits or intracellular cysts is pathognomic. Mutations in TGFBI are responsible for superficial and stromal corneal dystrophies. The gene product, transforming growth factor β induced protein (TGFBIp) accumulates as insoluble deposits in various forms. The severity, clinicopathogenic variations, age of the onset, and location of the deposits depend on the type of amino acid alterations in the protein. Until 2006, 38 different pathogenic mutants were reported for the TGFBI-associated corneal dystrophies. This number has increased to 63 mutants, reported in more than 30 countries. There is no effective treatment to prevent, halt, or reverse the deposition of TGFBIp. This review presents a complete mutation update, classification of phenotypes, comprehensive reported incidents of various mutations, and current treatment options and their shortcomings. Future research directions and possible approaches to inhibiting disease progression are discussed.
authors.affiliation: Singapore Eye Research Institute, Singapore; SRP Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore.
authors.forename: R
authors.initials: R
authors.lastname: Lakshminarayanan
authors.affiliation: Singapore Eye Research Institute, Singapore; SRP Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Chaurasia
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Venkatraman
authors.initials: V
authors.lastname: Anandalakshmi
authors.affiliation: Singapore Eye Research Institute, Singapore; Singapore National Eye Centre, Singapore.
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Chai
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Elavazhagan
authors.initials: E
authors.lastname: Murugan
authors.affiliation: Singapore Eye Research Institute, Singapore; SRP Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Eranga N
authors.initials: EN
authors.lastname: Vithana
authors.affiliation: Singapore Eye Research Institute, Singapore; SRP Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Beuerman
authors.affiliation: Singapore Eye Research Institute, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Singapore National Eye Centre, Singapore; Department of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore. Electronic address: jodmehta@gmail.com.
authors.forename: Jodhbir S
authors.initials: JS
authors.lastname: Mehta
mesh_terms: D003315:Cornea / Q000378:metabolism*; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D000099222:betaIG-H3 Protein
chemical_list: D004247:DNA; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein
keywords: IC3D classification; TGFBI; amyloid; corneal dystrophy; granular corneal dystrophy; lattice corneal dystrophy; transforming growth factor β