Uemichi T, Liepnieks J J, Benson M D
Department of Medicine, Indiana University, Indianapolis.
J Clin Invest. 1994 Feb;93(2):731-6. doi: 10.1172/JCI117027.
Two families with hereditary renal amyloidosis were found to have a novel mutation in the fibrinogen A alpha chain gene. This form of amyloidosis is an autosomal dominant condition characterized by proteinuria, hypertension, and subsequent azotemia. DNAs of patients with amyloidosis were screened for a polymorphism in fibrinogen A alpha chain gene by single-strand conformation polymorphism analysis, and affected individuals from two kindreds were found to have a mutation. Both of these kindreds are American of Irish descent presenting with non-neuropathic, nephropathic amyloidosis in the fifth to the seventh decade of life. DNA sequencing showed a point mutation in the fibrinogen A alpha chain gene that is responsible for substitution of valine for glutamic acid at position 526. By restriction fragment length polymorphism analysis, 7 affected individuals and 14 asymptomatic individuals in these two kindreds were positive for the fibrinogen A alpha chain Val 526 gene. Fibrinogen was isolated from plasma of a heterozygous gene carrier and shown to contain approximately 50% variant fibrinogen. Discovery of this new mutation confirms the association between fibrinogen A alpha chain variant and hereditary renal amyloidosis and establishes a new biochemical subtype of amyloidosis.
发现两个遗传性肾淀粉样变性家族在纤维蛋白原Aα链基因中存在一种新的突变。这种淀粉样变性形式是一种常染色体显性疾病，其特征为蛋白尿、高血压及随后出现的氮质血症。通过单链构象多态性分析对淀粉样变性患者的DNA进行纤维蛋白原Aα链基因多态性筛查，发现来自两个家族的患病个体存在突变。这两个家族均为爱尔兰裔美国人，在50至70岁时出现非神经性、肾病性淀粉样变性。DNA测序显示纤维蛋白原Aα链基因存在一个点突变，该突变导致第526位的谷氨酸被缬氨酸取代。通过限制性片段长度多态性分析，这两个家族中的7名患病个体和14名无症状个体的纤维蛋白原Aα链Val 526基因呈阳性。从一名杂合基因携带者的血浆中分离出纤维蛋白原，结果显示其含有约50%的变异纤维蛋白原。这一新突变的发现证实了纤维蛋白原Aα链变异与遗传性肾淀粉样变性之间的关联，并确立了一种新的淀粉样变性生化亚型。
