Sunada Y, Nakase H, Shimizu T, Mannen T, Kanazawa I
Department of Neurology, Faculty of Medicine, University of Tokyo.
Rinsho Shinkeigaku. 1992 Aug;32(8):840-4.
Familial amyloidotic polyneuropathy type IV (FAP IV) is clinically characterized by slowly progressive cranial neuropathy and corneal lattice dystrophy. More than 300 cases were clustered in the Finnish population. Recent biochemical studies have demonstrated that the amyloid fibril protein in FAP IV is related to Asn-187 variant gelsolin, and the corresponding missense mutation, a G to A substitution at nucleotide 654 of plasma gelsolin cDNA, cosegregates with the disease phenotype in Finnish families. Here we analyzed the gelsolin gene of the Japanese family with FAP IV which we described as the first Japanese case. Direct sequence analysis of PCR-amplified DNA fragments spanning the codon 187 of plasma gelsolin cDNA from the 2 affected family members demonstrated a single base substitution, G to A at nucleotide 654, which is identical to the mutation of Finnish FAP IV. Restriction analysis using a modified PCR revealed that three unaffected family members and three unrelated healthy controls were homozygous for the normal allele, whereas the seven affected family members were heterozygous for the normal and the mutated alleles. This indicates the cosegregation of the mutation with the disease phenotype in this Japanese family, suggesting that the mutation causes the FAP IV phenotype regardless of ethnic background.
IV型家族性淀粉样多神经病（FAP IV）的临床特征为缓慢进展的颅神经病变和角膜格子状营养不良。300多例病例集中在芬兰人群中。最近的生化研究表明，FAP IV中的淀粉样纤维蛋白与Asn-187变体凝溶胶蛋白有关，相应的错义突变，即血浆凝溶胶蛋白cDNA第654位核苷酸由G到A的替换，在芬兰家族中与疾病表型共分离。在此，我们分析了我们描述为日本首例的患有FAP IV的日本家族的凝溶胶蛋白基因。对来自2名受影响家族成员的跨越血浆凝溶胶蛋白cDNA第187密码子的PCR扩增DNA片段进行直接序列分析，结果显示在第654位核苷酸处有一个单碱基替换，由G变为A，这与芬兰FAP IV的突变相同。使用改良PCR进行的限制性分析表明，3名未受影响的家族成员和3名无关健康对照为正常等位基因纯合子，而7名受影响的家族成员为正常和突变等位基因杂合子。这表明该突变在这个日本家族中与疾病表型共分离，提示无论种族背景如何，该突变都会导致FAP IV表型。
