de la Chapelle A, Kere J, Sack G H, Tolvanen R, Maury C P
Department of Medical Genetics, University of Helsinki, Finland.
Genomics. 1992 Jul;13(3):898-901. doi: 10.1016/0888-7543(92)90182-r.
The Finnish type of familial amyloid polyneuropathy (FAF) is an autosomal dominant form of systemic amyloidosis caused by a mutation in the gelsolin gene. The mutation leads to the expression of amyloidogenic mutant Asp187----Asn gelsolin, an actin-modulating protein. We previously developed a DNA test based on amplification by the polymerase chain reaction followed by allele-specific oligonucleotide hybridization that identifies the base substitution adenine for guanine at nucleotide 654 in the gelsolin gene causing the disease. We show here that the same mutation is present in members of six apparently unrelated Finnish families and in a member of an unrelated American family. These results, taken together with previously published findings in nine additional Finnish families and another unrelated American family, indicate that most, perhaps all, FAF patients in Finland and possibly worldwide carry the same mutation. We suggest two alternative explanations: (i) the mutation arose in a very early common ancestor or (ii) the Asn187 mutation is particularly, perhaps uniquely, amyloidogenic.
芬兰型家族性淀粉样多神经病（FAF）是一种常染色体显性遗传的全身性淀粉样变性疾病，由凝溶胶蛋白基因突变引起。该突变导致淀粉样变突变体天冬氨酸187→天冬酰胺凝溶胶蛋白的表达，这是一种肌动蛋白调节蛋白。我们之前开发了一种基于聚合酶链反应扩增、随后进行等位基因特异性寡核苷酸杂交的DNA检测方法，该方法可识别凝溶胶蛋白基因第654位核苷酸处导致该疾病的鸟嘌呤被腺嘌呤取代的碱基替换。我们在此表明，六个明显无亲缘关系的芬兰家族成员以及一个无亲缘关系的美国家族成员中存在相同的突变。这些结果，与之前在另外九个芬兰家族和另一个无亲缘关系的美国家族中发表的研究结果一起，表明芬兰以及可能全球的大多数（也许是所有）FAF患者都携带相同的突变。我们提出两种可能的解释：（i）该突变出现在一个非常早期的共同祖先中；（ii）天冬酰胺187突变特别（也许是唯一）具有淀粉样变性。
