Purpose: This study investigated patients with granular dystrophy and identified a homozygotic patient and his family with a mutation in the betaig-h3 gene.
Methods: Genomic DNAs were extracted from leukocytes of the peripheral blood of the proband, his parents, and his grandmother. All had granular dystrophy. Genomic DNAs from 50 unrelated normal volunteers were used as controls. Exon 4 of betaig-h3 gene was amplified and analyzed by direct sequence. Clinical data were collected.
Results: A single-base-pair transition was detected. This was a substitution of G to A of the second nucleotide position of codon 124 in the betaig-h3 gene that led to a replacement of histidine for arginine (Arg124His, CGC-->CAC). This mutation was the precise one previously reported for Avellino dystrophy. Although the proband was homozygotic for the mutant alleles, his grandmother, and parents were heterozygotic for these alleles. No sequence modification in the codon 124 from 50 nonaffected control individuals was detected. Clinical findings of the proband were severe. Keratectomies were performed for both his eyes 5 times for a 24-year period. His grandmother and parents showed mild clinical symptoms, had a few annular granules in the subepithelial stroma, and maintained good visual acuities.
Conclusion: Arg124His mutation of the betaig-h3 gene was found in a pedigree with granular dystrophy. This mutation was the precise one previously reported for Avellino dystrophy. This fact shows an existence of Avellino form in Japanese. Homozygotic patient for mutant gene showed severe symptoms and an early onset.