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.
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Acknowledgments
We thank the patients and the family members for their participation in this study. This work was supported in part by KAKENHI (Grant-in-Aid for Scientific Research on Innovative Areas), Global COE Program, Integrated Database Project, and Scientific Research (A) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and a Grant-in-Aid for Research on Intractable Diseases and Comprehensive Research on Disability Health and Welfare from the Ministry of Health, Welfare and Labour, Japan.
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Taira, M., Ishiura, H., Mitsui, J. et al. Clinical features and haplotype analysis of newly identified Japanese patients with gelsolin-related familial amyloidosis of Finnish type. Neurogenetics 13, 237–243 (2012). https://doi.org/10.1007/s10048-012-0330-0
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DOI: https://doi.org/10.1007/s10048-012-0330-0