Benson M D, Liepnieks J, Uemichi T, Wheeler G, Correa R
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Nat Genet. 1993 Mar;3(3):252-5. doi: 10.1038/ng0393-252.
Three members of a family who died with renal amyloidosis were found to share a single nucleotide substitution in the fibrinogen alpha-chain gene. The predicted arginine to leucine mutation (Arg554Leu) was proven by amino acid sequence analysis of amyloid fibril protein isolated from postmortem kidney of an affected individual. Direct genomic DNA sequencing and restriction fragment length polymorphism analysis demonstrated that all three affected individuals had the guanine to thymine 4993 transversion. This is the first demonstration of hereditary amyloidosis associated with a variant fibrinogen alpha-chain. Variants of circulating fibrinogen may be the cause of a number of systemic amyloidoses with primarily renal involvement.
一个死于肾淀粉样变性的家族中的三名成员被发现纤维蛋白原α链基因存在单核苷酸替换。通过对一名患病个体死后肾脏中分离出的淀粉样纤维蛋白进行氨基酸序列分析，证实了预测的精氨酸到亮氨酸突变（Arg554Leu）。直接基因组DNA测序和限制性片段长度多态性分析表明，所有三名患病个体都存在4993位鸟嘌呤到胸腺嘧啶的颠换。这是首次证明与纤维蛋白原α链变体相关的遗传性淀粉样变性。循环纤维蛋白原的变体可能是许多主要累及肾脏的系统性淀粉样变性的病因。
