HEREDITARY RENAL AMYLOIDOSIS WITH A NOVEL VARIANT FIBRINOGEN
HEREDITARY RENAL AMYLOIDOSIS WITH A NOVEL VARIANT FIBRINOGEN
复制标题
DOI：
10.1172/jci117027
复制
发表时间：
1994-02-01
影响因子：
15.9
通讯作者：
BENSON, MD
中科院分区：
文献类型：
--
作者：
UEMICHI, T;LIEPNIEKS, JJ;BENSON, MD
发现两个遗传性肾淀粉样变家系在纤维蛋白原A α链基因上有一个新的突变。这种淀粉样变性是一种常染色体显性疾病，其特征是蛋白尿、高血压和随后的氮质血症。通过单链构象多态性分析，对淀粉样变性患者的DNA进行了纤维蛋白原A α链基因多态性的筛查，发现两种激酶的受累个体都有突变。这两例患者均为爱尔兰裔美国人，在5 ~ 70岁时表现为非神经性肾病性淀粉样变性。DNA测序显示纤维蛋白原A α链基因中的点突变，其负责在位置526处将缬氨酸替换为谷氨酸。经限制性片段长度多态性分析，两组患者中7例患者和14例无症状者的纤维蛋白原A α链瓦尔526基因均为阳性。从一个杂合基因携带者血浆中分离出纤维蛋白原，发现其含有约50%的变异型纤维蛋白原，证实了纤维蛋白原A α链变异与遗传性肾淀粉样变的相关性，并建立了淀粉样变的一个新的生化亚型。
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 nonneuropathic, 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 similar to 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.