Purpose. This study investigated patients with granular dystrophy and
identified a homozygotic patient and his family with a mutation in the
beta ig-h3 gene. Methods. Genomic DNAs were extracted from leukocytes
of the peripheral blood of the proband, his parents, and his grandmot
her. All had granular dystrophy. Genomic DNAs from 50 unrelated normal
volunteers were used as controls. Exon 4 of beta ig-h3 gene was ampli
fied and analyzed by direct sequence. Clinical data were collected. Re
sults. A single-base-pair transition was detected. This was a substitu
tion of G to A of the second nucleotide position of codon 124 in the b
eta ig-h3 gene that led to a replacement of histidine for arginine (Ar
g124His, CGC --> CAC). This mutation was the precise one previously re
ported for Avellino dystrophy. Although the proband was homozygotic fo
r the mutant alleles, his grandmother, and parents were heterozygotic
for these alleles. No sequence modification in the codon 124 from 50 n
onaffected 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 cl
inical symptoms, had a few annular granules in the subepithelial strom
a, and maintained good visual acuities. Conclusion. Arg124His mutation
of the beta ig-h3 gene was found in a pedigree with granular dystroph
y. 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 earl
y onset.