Avellino Corneal Dystrophy in an African-American

Abstract

Abstract: : Purpose: Granular-lattice (Avellino) corneal dystrophy is a rare condition reported in individuals of Italian descent, and more recently, in European and Asian family members. Missense mutations in the ßig-h3 gene (growth factor gene, perhaps active in cell adhesion) on chromosome5q31 cause four distinct autosomal dominant corneal dystrophies, including Avellino. We report a case of Avellino corneal dystrophy in an African-American. Methods: Clinical records and histopathologic findings of the patient were reviewed. The patient's bilateral corneal buttons were stained with hematoxylin and eosin, PAS, Masson's trichrome, and alkaline Congo red stains using standard methods. After informed consent was obtained, the patient donated a blood sample from which leukocyte DNA was amplified by the polymerase chain reaction. We evaluated first the exons previously reported to contain mutations: exon 4 (codon 124), exon 11 (codon 501), exon 12 (codons 518, 527, 540, 555), and exon 14 (codons 623, 626). The primers used are listed below. PCR products were gel purified and cloned into pCR4-TOPO TA cloning vector (Invitrogen, USA). Purified plasmid DNA was sequenced with Epicentre Technologies Excel II kit for Licor automated sequencers using dye-labeled primers. Results: Patchy subepithelial hyaline deposits stained bright red with Masson's trichrome stain indicative of granular dystrophy. Deep stromal amyloid deposits could be shifted from red to apple green in the Congo red stained sections indicative of lattice dystrophy. The deposits are negative for PAS, Alcian blue, and trichrome. Combined cornea deposits, hyaline (subepithelial) and amyloid (anterior and deep stromal) are suggestive of atypical granular-lattice dystrophy (Avellino). Sequences of exons 11, 12, and 14 were all wild type DNA without recognizable mutations. Mutations previously reported in granular dystrophy Arg555Trp (exon 12), lattice dystrophy Leu527Arg (exon 12) and His626Arg (exon 14) and Reis-Bucklers dystrophy Glyc623Asp (exon 14) and Phe540 (exon 12) were not observed. Exon 4 contained a C to T mutation in position 1 of codon 124, changing an arginine to cysteine (not the Arg124His mutation previously reported in Avellino). This mutation had previously been reported in lattice dystrophy. Conclusions: Clinicohistopathological diagnosis of Avellino dystrophy has been found in a wider racial background than has previously been reported in the literature. Subsequent sequencing of DNA indicated a Arg124Cys mutation in the ßig-h3 gene.

Keywords: degenerations/dystrophies