title: Clinical features and haplotype analysis of newly identified Japanese patients with gelsolin-related familial amyloidosis of Finnish type.
abstract: 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.
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Taira
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ishiura
authors.forename: Jun
authors.initials: J
authors.lastname: Mitsui
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hayashi
authors.forename: Jun
authors.initials: J
authors.lastname: Shimizu
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsukawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Saito
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Okada
authors.forename: Sadatoshi
authors.initials: S
authors.lastname: Tsuji
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Sawamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Amano
authors.forename: Jun
authors.initials: J
authors.lastname: Goto
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis* / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D018260:Gelsolin / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: D018260:Gelsolin