Saraiva M J, Almeida M R, Alves I L, Moreira P, Gawinowicz M, Costa P P, Rauh S, Banhzoff A, Altland K
Centro de Estudos de Paramiloidose, Hospital de Santo António, Porto, Portugal.
Am J Hum Genet. 1991 May;48(5):1004-8.
A mutation in transthyretin (TTR Asn 90) has been identified in the Portuguese and German populations. This variant has a lower pI and was found by screening analyses in 2/4,000 German subjects and in 4/1,200 Portuguese by using either double one-dimensional (D1-D) electrophoresis with isoelectric focusing (IEF) or hybrid isoelectric focusing in immobilized pH gradient (HIEF) as the final separation step. The Portuguese population sample was from the area where TTR Met 30-associated familial amyloidotic polyneuropathy (FAP) prevails, and it was divided into (a) a group of 500 individuals belonging to FAP kindreds and (b) a group of 700 collected at random. HIEF showed two particular situations: (1) one case, from an FAP kindred, was simultaneously carrier of the Met 30 substitution and the acidic variant, and (2) one individual, from the randomly selected Portuguese sample, had only the acidic monomer. Comparative peptide mapping, by HPLC, of the acidic variant carriers and of normal TTR showed the presence of an abnormal tryptic peptide, not present in the normal TTR digests, with an asparagine-for-histidine substitution at position 90 explained by a single base change of adenine for cytosine in the histidine codon. This was confirmed at the DNA level by RFLP analyses of PCR-amplified material after digestion with SphI and BsmI. In all carriers of the Asn 90 substitution, no indicators were found for an association with traits characteristic for FAP.
在葡萄牙和德国人群中已鉴定出转甲状腺素蛋白（TTR Asn 90）的一种突变。该变体的等电点较低，通过使用等电聚焦（IEF）的双向一维（D1-D）电泳或固定化pH梯度中的混合等电聚焦（HIEF）作为最终分离步骤，在2/4000名德国受试者和4/1200名葡萄牙人中进行筛查分析时发现了这种变体。葡萄牙人群样本来自TTR Met 30相关的家族性淀粉样多神经病（FAP）盛行的地区，该样本分为（a）一组属于FAP家族的500人个体和（b）一组随机收集的700人。HIEF显示出两种特殊情况：（1）一例来自FAP家族的个体同时是Met 30替代和酸性变体的携带者，（2）一名来自随机选择的葡萄牙样本的个体仅具有酸性单体。通过HPLC对酸性变体携带者和正常TTR进行比较肽图分析，结果显示存在一种异常的胰蛋白酶肽，在正常TTR消化物中不存在，90位的组氨酸被天冬酰胺替代，这是由于组氨酸密码子中的腺嘌呤被胞嘧啶单碱基改变所致。在用SphI和BsmI消化后，通过对PCR扩增材料进行RFLP分析在DNA水平上证实了这一点。在所有Asn 90替代的携带者中，未发现与FAP特征性性状相关的指标。
