CORNEAL DYSTROPHY, PUNCTATE OR NODULAR
GRANULAR CORNEAL DYSTROPHY, TYPE I
GCDI
CDGG1
GCD1
Granular corneal dystrophy type 1
Corneal dystrophy Groenouw type I
Classic GCD
Classic granular corneal dystrophy
Granular corneal dystrophy was described by Groenouw (1890, 1898, 1917). Groenouw (1933) described the disorder in an autosomal dominant pattern through 4 generations. In the macular, granular, and lattice dystrophies, the changes are in the corneal stroma rather ... Granular corneal dystrophy was described by Groenouw (1890, 1898, 1917). Groenouw (1933) described the disorder in an autosomal dominant pattern through 4 generations. In the macular, granular, and lattice dystrophies, the changes are in the corneal stroma rather than the epithelium. In the granular and the lattice types, the histologic findings are hyaline degeneration with absence of acid mucopolysaccharide deposition. See corneal dystrophy, macular type (Groenouw type II; 217800). The opacity in the granular type consists of grayish white granules with sharp borders mainly in a disc-shaped area in the center of the cornea. The peripheral cornea is usually clear and the cornea between granules is clear. Hyaline material separates the epithelium from Bowman membrane. Although this type can have its onset in the first 10 years, visual acuity during childhood is usually good. Forsius (1981) stated that he had observed a Finnish family in which onset was between age 15 and 20 years; see Forsius et al. (1983). Although Forsius (1981) suggested that this might represent a special 'Finnish type,' with a very mild course and good prognosis, Moller (1989, 1991) concluded that the disorder did not differ from that in patients in other countries or from the description by Groenouw (1933). In an offspring of a first-cousin marriage with both parents mildly affected, Moller and Ridgway (1990) observed severe granular corneal dystrophy which they suggested might represent the homozygous state. Because of early onset and severe course, 2 corneal grafts in each eye were required before the age of 17. Family I, studied by Moller (1990), comprised 94 patients in 7 generations, of whom 75 were alive at the time of study. Abnormalities were confined to the eye. All patients developed cataract late in life. Corneal grafts remained clear. Moller (1990) reported a total of 5 Danish families, all showing autosomal dominant inheritance. Moller (1989) concluded that Reis-Bucklers corneal dystrophy may be the same entity as Groenouw type I granular corneal dystrophy.
Munier et al. (1997) generated a YAC contig of the linked area and, following cDNA selection, recovered the gene that encodes keratoepithelin. In 6 families they identified missense mutations. All detected mutations occurred at the CpG dinucleotide of ... Munier et al. (1997) generated a YAC contig of the linked area and, following cDNA selection, recovered the gene that encodes keratoepithelin. In 6 families they identified missense mutations. All detected mutations occurred at the CpG dinucleotide of 2 arginine codons: R555W in a CDGG1 family (601692.0001), R555Q in a CDTB family (601692.0002), R124C in 2 CDL1 families (601692.0003), and R124H in 2 ACD families (601692.0004). As the last 2 sequences are characterized by amyloid deposits, Munier et al. (1997) concluded that the R124-mutated keratoepithelin forms amyloidogenic intermediates that precipitate in the cornea. The observations established a common molecular origin of the four 5q31-linked corneal dystrophies. Kim et al. (2002) studied the molecular properties of wildtype and mutant BIGH3 proteins: specifically, the arg124-to-leu (R124L; 601692.0007) (CDRB), R124C (CDL1), R124H (ACD), R555W (CDGG1), and R555Q (CDTB) mutations commonly found in 5q31-linked corneal dystrophies. They found that the mutations did not significantly affect the fibrillar structure, interactions with other extracellular matrix proteins, or adhesion activity in cultured corneal epithelial cells. In addition, the mutations apparently produced degradation products similar to those of wildtype BIGH3. BIGH3 polymerizes to form a fibrillar structure and strongly interacts with type I collagen (see 120150), laminin (see 150320), and fibronectin (135600). Mutations did not significantly affect these properties. Kim et al. (2002) concluded that mutant forms of BIGH3 might require other cornea-specific factors to form the abnormal accumulations seen in 5q31-linked corneal dystrophies.