Uemichi T, Liepnieks J J, Yamada T, Gertz M A, Bang N, Benson M D
Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
Blood. 1996 May 15;87(10):4197-203.
A new American kindred with amyloidosis was found by single-strand conformation polymorphism analysis to have a mutation in the fibrinogen A alpha chain gene. Affected members in this kindred have autosomal dominant amyloid nephropathy. DNA sequencing showed a single nucleotide deletion at the third base of codon 524 of the fibrinogen A alpha chain genes (4904delG) that resulted in a frame shift and premature termination of the protein at codon 548. Antiserum was produced to a portion of the abnormal peptide predicted by the DNA sequence and amyloid deposits were immuno-histologically proven to contain this abnormal peptide. Two of the propositus' 4 children were positive for the mutant fibrinogen A alpha chain gene by restriction fragment length polymorphism analysis based on polymerase chain reaction. These two mutant gene carriers now in the second decade of life show no clinical symptoms of amyloidosis as yet but have lower plasma fibrinogen concentrations when compared with their normal siblings. This the first description of a kindred with renal amyloidosis and low plasma fibrinogen and also the first report of amyloidosis caused by a frame shift mutation.
通过单链构象多态性分析发现一个新的患有淀粉样变性的美国家族，其纤维蛋白原Aα链基因存在突变。该家族中的患病成员患有常染色体显性遗传性淀粉样肾病。DNA测序显示，纤维蛋白原Aα链基因第524密码子的第三个碱基处发生单核苷酸缺失（4904delG），导致移码并使蛋白质在第548密码子处提前终止。针对DNA序列预测的部分异常肽制备了抗血清，免疫组织学证实淀粉样沉积物中含有这种异常肽。先证者的4个孩子中有2个通过基于聚合酶链反应的限制性片段长度多态性分析，检测出突变的纤维蛋白原Aα链基因呈阳性。这两名处于第二个十年生活期的突变基因携带者目前尚无淀粉样变性的临床症状，但与正常的兄弟姐妹相比，其血浆纤维蛋白原浓度较低。这是对一个患有肾淀粉样变性且血浆纤维蛋白原水平低的家族的首次描述，也是由移码突变引起的淀粉样变性的首次报道。
