Paunio T, Sunada Y, Kiuru S, Makishita H, Ikeda S, Weissenbach J, Palo J, Peltonen L
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Hum Mutat. 1995;6(1):60-5. doi: 10.1002/humu.1380060112.
Familial amyloidosis, Finnish type (FAF) (gelsolin-related amyloidosis) is an autosomal dominant form of systemic amyloidosis characterized by corneal lattice dystrophy and peripheral polyneuropathy. The accumulating protein in FAF consists of fragments of gelsolin, an actin-modulating protein. The gelsolin mutation G654A has been found in both Finnish and Japanese patients. To study the origin of the gelsolin mutation in these patients we performed haplotype analysis in 10 Finnish and 2 Japanese FAF families. Poymorphic DNA markers GSN, D9S103, AFMa061xd9, and AFMa139xb9 revealed a uniform disease haplotype in all the disease-associated chromosomes of the Finnish FAF families, which was different from the one observed in the Japanese families. The present results and the previously detected gelsolin mutation G654T in Czech and Danish FAF patients suggest that nucleotide 654 may represent a mutation hot spot in the gelsolin gene. The DNA markers studied here will be useful in future genealogical analyses of FAF.
芬兰型家族性淀粉样变性（FAF）（凝溶胶蛋白相关性淀粉样变性）是一种常染色体显性全身性淀粉样变性，其特征为角膜格子状营养不良和周围性多神经病。FAF中蓄积的蛋白由肌动蛋白调节蛋白凝溶胶蛋白的片段组成。在芬兰和日本患者中均发现了凝溶胶蛋白突变G654A。为研究这些患者中凝溶胶蛋白突变的起源，我们对10个芬兰FAF家族和2个日本FAF家族进行了单倍型分析。多态性DNA标记GSN、D9S103、AFMa061xd9和AFMa139xb9在芬兰FAF家族所有与疾病相关的染色体上均显示出一致的疾病单倍型，这与在日本家族中观察到的单倍型不同。目前的结果以及先前在捷克和丹麦FAF患者中检测到的凝溶胶蛋白突变G654T表明，核苷酸654可能是凝溶胶蛋白基因中的一个突变热点。此处研究的DNA标记将有助于未来对FAF进行系谱分析。
