Nakazato M, Matsukura S
Third Department of Internal Medicine, Miyazaki Medical College.
Nihon Ronen Igakkai Zasshi. 2001 Jul;38(4):501-6. doi: 10.3143/geriatrics.38.501.
We have identified that familial amyloid polyneuropathy with middle age onset results from missense mutations of the transthyretin gene. In the present study, we investigated molecular abnormalities of transthyretin in elderly patients with cardiac amyloidosis or amyloid polyneuropathy, using DNA sequencing and protein sequencing. We detected 5 cases of transthyretin-related cardiac amyloidosis using immunohistochemical techniques. All of them had late-onset, mild or no peripheral neuropathy or autonomic dysfunctions, and no family history. Three had transthyretin Met30 and two transthyretin Ile50. We also found 15 patients with transthyretin-related amyloid polyneuropathy. All of them had late-onset and no contributory family history. Twelve had transthyretin Met30, two transthyretin Ile50, and one transthyretin Ser109. Clinical manifestations and sequencing procedures of six representative patients were also presented. Molecular investigation of transthyretin is needed for elderly patients with etiology-unknown cardiac amyloidosis or amyloid polyneuropathy even if there is no family history of amyloidosis.
我们已确定中年起病的家族性淀粉样多神经病是由转甲状腺素蛋白基因突变导致的错义突变引起。在本研究中，我们使用DNA测序和蛋白质测序技术，对老年心脏淀粉样变性或淀粉样多神经病患者的转甲状腺素蛋白分子异常情况进行了调查。我们采用免疫组化技术检测出5例转甲状腺素蛋白相关的心脏淀粉样变性病例。所有患者均为迟发性，有轻度或无周围神经病变或自主神经功能障碍，且无家族史。其中3例为转甲状腺素蛋白Met30，2例为转甲状腺素蛋白Ile50。我们还发现了15例转甲状腺素蛋白相关的淀粉样多神经病患者。所有患者均为迟发性，且无家族病史。其中12例为转甲状腺素蛋白Met30，2例为转甲状腺素蛋白Ile50，1例为转甲状腺素蛋白Ser109。还介绍了6例代表性患者的临床表现和测序过程。对于病因不明的老年心脏淀粉样变性或淀粉样多神经病患者，即使没有淀粉样变性家族史，也需要对转甲状腺素蛋白进行分子研究。
