Congenital afibrinogenemia: identification and expression of a missense mutation in FGB impairing fibrinogen secretion.
Congenital afibrinogenemia: identification and expression of a missense mutation in FGB impairing fibrinogen secretion.
复制标题
先天性无纤维蛋白原血症：FGB 中损害纤维蛋白原分泌的错义突变的鉴定和表达。
作者：
D. Vũ;P. Bolton;J. Parr;M. Morris;P. de Moerloose;M. Neerman
先天性无纤维蛋白原血症是一种罕见的常染色体隐性遗传病，其特征是完全缺乏可检测到的纤维蛋白原。我们之前发现了这种疾病的第一个致病突变：大约11kb的纤维蛋白原阿尔法链基因(FGA)的纯合子缺失。随后的研究表明，绝大多数无纤维蛋白原血症突变位于FGA中，但FGG和FGB中也发现了突变。除在FGB的C末端发现3个错义突变外，所有导致无纤维蛋白原血症的纤维蛋白原基因突变均为零。在本研究中，一名患有纤维蛋白原血症的男孩被发现是FGB两个突变的复合杂合子：一个N端无义突变W47X(外显子2)和一个错义突变(G444S，外显子8)。FGB G444S突变基因与野生型FGA和FGG cDNA的共表达表明，含有突变β链的纤维蛋白原分子能够组装，但不能分泌到培养基中，证实了所鉴定突变的致病性质。
Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by complete absence of detectable fibrinogen. We previously identified the first causative mutations for this disease: a homozygous deletion of approximately 11 kb of the fibrinogen alpha-chain gene (FGA). Subsequent studies revealed that the great majority of afibrinogenemia mutations are localized in FGA, but mutations were also found in FGG and FGB. Apart from 3 missense mutations identified in the C-terminal portion of FGB, all fibrinogen gene mutations responsible for afibrinogenemia are null. In this study, a young boy with afibrinogenemia was found to be a compound heterozygote for 2 mutations in FGB: an N-terminal nonsense mutation W47X (exon 2) and a missense mutation (G444S, exon 8). Coexpression of the FGB G444S mutant cDNA in combination with wild-type FGA and FGG cDNAs demonstrated that fibrinogen molecules containing the mutant beta chain are able to assemble but are not secreted into the media, confirming the pathogenic nature of the identified mutation.
DOI：
10.1073/pnas.82.8.2344
发表时间：
1985-01-01
影响因子：
11.1
作者：
KANT, JA;FORNACE, AJ;CRABTREE, GR
通讯作者：
CRABTREE, GR