Clinical Features and Haplotype Analysis of Newly Identified Japanese Patients with Gelsolin-related Familial Amyloidosis of Finnish Type

Familial amyloidosis of the Finnish type (FAF) is an autosomal dominant form of systematic amyloidosis characterized by lattice corneal dystrophy, cranial neuropathy, and cutis laxa. Although FAF has been frequently found in the Finnish population, FAF is a considerably rare disorder in other regions. In this study, we examined the clinical characteristics as well as the haplotypes of six Japanese patients with FAF from five families. They showed the typical clinical presentations of FAF, but we found a broad range of ages at onset of neurological symptoms. All members had the c.654G>A mutation in GSN. To evaluate the disease haplotypes, high-density single-nucleotide polymorphism (SNP) arrays were used and disease-relevant haplotypes were reconstructed. Haplotype analysis in the four apparently unrelated families suggested a common founder haplotype. In a sporadic FAF patient, however, the haplotype was dissimilar to the founder haplotype. The present study demonstrated that a founder mutation in most of the Japanese families with FAF, except for a sporadic patient in whom a de novo mutation event was suggested as the origin of the mutation.