title: Genetics of anterior and stromal corneal dystrophies.
abstract: Corneal dystrophies are a group of heterogenous conditions that are characterized by the progressive loss of corneal transparency that results from the accumulation of deposits within the different corneal layers. Up until recently, corneal dystrophies were classified according to their slit lamp appearance, the morphology of the deposits, the depth of the corneal involvement and their histopathological features. This classification has been challenged because of the significant inter-and intra- familial variability in phenotypic expression of the corneal dystrophies and the overlapping characteristics between the different types. In addition, there are dystrophies with atypical characteristics that involve multiple corneal layers or are associated with extraocular involvement that can not be classified into a single type based on morphologic criteria. Recent developments in corneal genetics have shed light on the pathogenesis of corneal dystrophies and have led to the implementation of a new classification scheme that takes into account the responsible gene defect. The discovery that mutations in Tissue Growth factor beta inducible (TGFBI) responsive gene, BIGH3, are the cause of a group of corneal dystrophies (granular, Avellino, lattice and Reis Bucklers) has revolutionized our understanding of these conditions (Stone et al., 1994; Munier et al., 1997). Since this discovery, the genetic basis of many corneal dystrophies and a chromosomal locus for several others has been described. It has also been shown that mutations in the same gene can cause different phenotypes. The association of specific gene mutations with specific phenotypes has given the clinician the opportunity to use molecular genetic analysis to diagnose dystrophic corneal disorders. In parallel, characterization of the mutations responsible for different types of corneal dystrophies has expanded our knowledge regarding their genetic and inheritance patterns. The finding of a highly penetrant, dominantly inherited corneal dystrophy in an affected offspring of unaffected parents has confirmed the existence of spontaneous pathogenic mutations. Additionally, molecular analysis for pathogenetic mutations can confirm the diagnosis in cases with atypical presentations of corneal dystophies. On the other hand, we still know little about how interactions between the environment and the genetic composition affect the phenotype of these conditions. It is highly likely that even when our understanding of the molecular basis of the corneal dystrophies is complete, this knowledge will be used as an adjunct to clinical findings to make the diagnosis of a corneal dystrophy.
authors.affiliation: Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
authors.forename: Vasilliki
authors.initials: V
authors.lastname: Poulaki
authors.forename: Kathryn
authors.initials: K
authors.lastname: Colby
mesh_terms: D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D003319:Corneal Stroma / Q000473:pathology*; D019573:Epithelium, Corneal / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D006801:Humans; D016212:Transforming Growth Factor beta / Q000235:genetics; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein