Biochemical marker in familial amyloidotic polyneuropathy, Portuguese type. Family studies on the transthyretin (prealbumin)-methionine-30 variant.
Biochemical marker in familial amyloidotic polyneuropathy, Portuguese type. Family studies on the transthyretin (prealbumin)-methionine-30 variant.
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葡萄牙型家族性淀粉样变性多发性神经病的生化标志物。
DOI：
10.1172/jci112224
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Goodman,DS
中科院分区：
文献类型：
--
作者：
Saraiva,MJ;Costa,PP;Goodman,DS
在葡萄牙家族性淀粉样多发性神经病（FAP）患者中发现了一种甲状腺素运载蛋白变体，其30位的缬氨酸被甲硫氨酸取代[TTR（Met 30）]。开发了有效、快速、小规模和半微量（免疫印迹）程序，以确定个体受试者血浆中是否存在TTR（Met 30）。免疫印迹法仅使用0.10 ml血清，可作为筛选大量人群中TTR（Met 30）存在的可靠方法。在7个FAP激酶的家族研究中，TTR（Met 30）在41个无症状FAP后代中的21个中被发现，并且其存在与年龄或性别无关。因此，突变TTR分离按照已知的常染色体显性遗传方式的FAP。总血浆TTR水平没有减少无症状FAP后代谁是TTR（Met 30）的运营商，并没有观察到差异之间的运营商和非运营商的突变TTR。在无症状FAP后代中估计血浆中变异TTR与正常TTR的比率，与在FAP患者中发现的比率相似。相比之下，TTR（Met 30）在两名FAP患者的脑脊液样品中相对富集。这一发现的意义尚不清楚，但可能与FAP中淀粉样蛋白在神经系统中的优先沉积有关。进行了一项有限的研究，同时分析了20个FAP后代的储存（1975年收集）和新鲜血清，所有这些后代在1975年都没有症状。在每例受试者中，储存的血清样本和新鲜血清样本获得的结果一致。自1975年以来，这些受试者中有6例发生临床FAP;这些受试者均存在TTR（Met 30）。这几项研究强烈表明，血浆中TTR（Met 30）的存在构成了FAP在疾病临床前阶段的预测性生化标志物。图片
A transthyretin variant with a methionine for valine substitution at position 30 [TTR(Met30)] is found in Portuguese patients with familial amyloidotic polyneuropathy (FAP). Effective, rapid, small- and semimicro-scale (immunoblotting) procedures were developed to determine whether or not TTR(Met30) is present in the plasma of an individual subject. The immunoblotting procedure employs only 0.10 ml of serum and can serve as a reliable procedure for the screening of large numbers of persons for the presence of TTR(Met30). In family studies of seven FAP kindreds, TTR(Met30) was found in 21 out of 41 asymptomatic FAP offspring, and its presence was not related to either age or sex. Thus, the mutant TTR segregated in accordance with the known autosomal dominant mode of inheritance of FAP. Total plasma TTR levels were not reduced in asymptomatic FAP offspring who were carriers of TTR(Met30), and no difference was observed between carriers and noncarriers of the mutant TTR. The ratios of the variant to normal TTR in plasma were estimated in asymptomatic FAP offspring and were similar to those found in FAP patients. In contrast, TTR(Met30) was relatively enriched in cerebrospinal fluid samples from two FAP patients. The significance of this finding is not known, but might relate to the preferential deposition of amyloid in the nervous system in FAP. A limited study was conducted involving simultaneous analysis of both stored (collected in 1975) and fresh serum from 20 FAP offspring, all of whom had been asymptomatic in 1975. In every subject, the results obtained with the stored and the fresh serum samples were in agreement. Six of these subjects developed clinical FAP since 1975; TTR(Met30) was present in each of these subjects. These several studies strongly suggest that the presence of TTR(Met30) in plasma constitutes a predictive biochemical marker of FAP in the preclinical phase of the disease.Images