Ii S, Sommer S S
Department of Biochemistry and Molecular Biology, Mayo Clinic/Foundation, Rochester, MN 55905.
Hum Mol Genet. 1993 Aug;2(8):1303-5. doi: 10.1093/hmg/2.8.1303.
Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant disease due to mutations in the transthyretin (TTR) gene. Valine30-->methionine (TTR M30) is by far the most common mutation in patients with FAP. In a sample of 11 North American unrelated patients, we previously found that 6 had TTR M30. By utilizing double PASA, we could perform haplotype analysis despite the absence of DNA samples on relatives. The results indicate that at least four of the six patients with TTR M30 have different haplotypes, an observation that is surprising for North American patients in which the ostensible symptoms generally begin after the reproductive years. It is suggested that the most likely explanation is rapid selection against TTR M30 mutations by one of four possible mechanisms.
家族性淀粉样多神经病（FAP）是一种常染色体显性疾病，由转甲状腺素蛋白（TTR）基因突变引起。缬氨酸30→甲硫氨酸（TTR M30）是FAP患者中迄今为止最常见的突变。在11名北美无亲缘关系的患者样本中，我们之前发现6名患者有TTR M30。通过使用双重聚合酶链反应-等位基因特异性扩增法（double PASA），尽管没有亲属的DNA样本，我们仍可进行单倍型分析。结果表明，6名TTR M30患者中至少有4名具有不同的单倍型，这一观察结果对于北美患者来说令人惊讶，因为在北美患者中，明显症状通常在生育年龄之后才开始出现。有人提出，最可能的解释是通过四种可能机制之一对TTR M30突变进行快速选择。
