Mikkola H, Palotie A
Department of Clinical Chemistry, Helsinki University Central Hospital, Finland.
Semin Thromb Hemost. 1996;22(5):393-8. doi: 10.1055/s-2007-999037.
The knowledge of the molecular basis of factor XIII deficiency has improved significantly in recent years. Almost 20 different mutations have been described in the gene coding for the factor A-subunit and 3 mutations in the gene coding for the B-subunit. Half of the mutations in the factor XIIIa A-subunit gene are nonsense mutations that result in premature termination of translation. Three of them are frameshift mutations that are caused by minor deletions. Two of them are splicing mutations and 3 are stop mutations that are caused by single nucleotide substitutions. Ten of the mutations are missense mutations caused by nucleotide transitions leading to amino acid substitutions. In the factor XIII B-subunit gene, the 3 mutations are an amino acid substitution, a splicing mutation, and a trinucleotide insertion. These mutations explain the disease in the two families reported to have XIII B-subunit deficiency. In factor XIII A-subunit deficiency, the genetic defects have been characterized so far only in a minority of cases. In most of the reports of factor XIII A-subunit mutations, each family carries its own mutation/mutations. However, in some populations such as Finns and Arabs some enrichment of specific mutations has occurred. Some international migration of a few mutations has also been noted. The structural and functional effects of the mutations have been analyzed by studying the expression of the factor XIII subunits on mRNA and protein levels in vivo or in vitro, and by utilizing the three-dimensional model of crystallized factor XIII A-subunit in modeling of the missense mutations.
近年来，关于因子 XIII 缺乏症分子基础的知识有了显著提高。在编码因子 A 亚基的基因中已描述了近 20 种不同的突变，在编码 B 亚基的基因中有 3 种突变。因子 XIIIa A 亚基基因中的突变有一半是无义突变，导致翻译提前终止。其中 3 种是由小缺失引起的移码突变。2 种是剪接突变，3 种是由单核苷酸替换引起的终止突变。10 种突变是由核苷酸转换导致氨基酸替换的错义突变。在因子 XIII B 亚基基因中，3 种突变分别是氨基酸替换、剪接突变和三核苷酸插入。这些突变解释了报道的两个患有 XIII B 亚基缺乏症的家族中的疾病情况。在因子 XIII A 亚基缺乏症中，到目前为止仅在少数病例中明确了遗传缺陷。在大多数关于因子 XIII A 亚基突变的报道中，每个家族都有其自身的一个或多个突变。然而，在一些人群中，如芬兰人和阿拉伯人中，某些特定突变出现了富集现象。还注意到一些突变在国际间的迁移。通过在体内或体外研究因子 XIII 亚基在 mRNA 和蛋白质水平上的表达，并利用结晶的因子 XIII A 亚基的三维模型对错义突变进行建模，分析了这些突变的结构和功能影响。
