Heart failure caused by a novel amyloidogenic mutation of the transthyretin gene:: ATTR Ala45Ser
Heart failure caused by a novel amyloidogenic mutation of the transthyretin gene:: ATTR Ala45Ser
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DOI：
10.3109/13506120009146252
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发表时间：
2000-06-01
期刊：
影响因子：
--
通讯作者：
Tashima, K
中科院分区：
文献类型：
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作者：
Janunger, T;Anan, I;Tashima, K
甲状腺素运载蛋白（TTR）淀粉样变性患者的心力衰竭已被证明是由TTR基因的不同突变引起的。在本病例中，来自瑞典北方的一名73岁男性被评估为心力衰竭。在皮下脂肪和肠活检中发现淀粉样蛋白沉积。通过电喷雾电离质谱法（ESI-MS）在血浆中检测到TTR变体形式的存在。通过TTR基因的单链构象多态性（SSCP）分析定位突变，其中在外显子2中观察到条带移位。外显子2的直接测序显示一个单碱基对替换（G1724 T）。这种颠换导致密码子45处的氨基酸取代，丙氨酸变为丝氨酸（ATTRAla 45 Ser）。质谱分析排除了该变体是多态性，因为在200多个对照样品中不存在类似的分子量变化。十二指肠活检标本的刚果红和免疫染色证实了系统性ATTR淀粉样变性的存在，包括超声心动图在内的临床检查发现了限制性心肌病的证据。10年前，他曾因双侧腕管综合征接受手术，但除此之外，没有任何症状可归因于他的系统性淀粉样变性。在神经传导研究中未发现轴突性多神经病。这种新的突变是在瑞典人群中发现的第二种淀粉样TTR突变。
Cardiac failure in transthyretin (TTR) amyloidosis patients has been shown to be caused by different mutations in the TTR gene. In the present case, a 73-year-old man from Northern Sweden was evaluated for heart failure. Amyloid deposits were found in subcutaneous fat and in intestinal biopsies. The presence of a variant form of TTR was detected in the plasma by electrospray ionisation mass spectrometry (ESI-MS). The mutation was located by single-strand conformation polymorphism (SSCP) analysis of the TTR gene where a band shift was seen in exon 2. Direct sequencing of exon 2 revealed a single base-pair substitution (G1724T). This transversion results in an amino acid substitution at codon 45, alanine to serine (ATTRAla45Ser). Mass spectrometry analysis excluded that the variant is a polymorphism, since no similar shift in molecular weight has been present in more than 200 control samples. Congo red and immunostaining of duodenum biopsy specimens confirmed the presence of systemic ATTR amyloidosis, and clinical examination, including echocardiography, found evidence of a restrictive cardiomyopathy. He had 10 years previously been operated for a bilateral carpal tunnel syndrome, but otherwise no symptoms were present that could be attributed to his systemic amyloidosis. No axonal polyneuropathy was noted at nerve conduction studies. This novel mutation is the second amyloidogenic TTR mutation found in the Swedish population.