Inherited amyloid polyneuropathy type IV (gelsolin variant) in a Japanese family

We describe a Japanese family with familial amyloid polyneuropathy type IV. The family originates from central Japan, Nagano prefecture, and is unrelated to Finnish or other Caucasian populations. Of 42 members in three generations, 14 individuals (5 men, 9 women) are affected by corneal lattice dystrophy, cranial neuropathy, mild peripheral neuropathy, and skin changes. Polarizing microscopy and immunohistochemistry studies of skin biopsy samples demonstrated abundant amyloid deposits, which bound an antigelsolin monoclonal antibody. Direct sequence analysis of a DNA fragment spanning codon 187 of plasma gelsolin complementary DNA and restriction analysis using a modified polymerase chain reaction demonstrated a single base substitution, guanine to adenine, at nucleotide position 654, which is identical to the mutation in Finnish familial amyloid polyneuropathy type IV. This strongly suggests that the mutation causes the familial amyloid polyneuropathy type IV phenotype regardless of ethnic background.