Asakai R, Chung D W, Davie E W, Seligsohn U
Department of Biochemistry, University of Washington, Seattle 98195.
N Engl J Med. 1991 Jul 18;325(3):153-8. doi: 10.1056/NEJM199107183250303.
Severe factor XI deficiency, which is relatively common among Ashkenazi Jews, is associated with injury-related bleeding of considerable severity. Three point mutations--a splice-junction abnormality (Type I), Glu117----Stop (Type II), and Phe283----Leu (Type III)--have been described in six patients with factor XI deficiency. Clinical correlations with these mutations have not been carried out. We determined the relative frequency of the mutations and their association with plasma levels of factor XI clotting activity and bleeding, analyzing the mutations with the polymerase chain reaction and restriction-enzyme digestion.
The Type II and Type III mutations had similar frequencies among 43 Ashkenazi Jewish probands with severe factor XI deficiency; these two mutations accounted for 49 percent and 47 percent, respectively, of a total of 86 analyzed alleles. Among 40 of the probands and 12 of their relatives with severe factor XI deficiency, patients homozygous for Type III mutation had a significantly higher level of factor XI clotting activity (mean [+/- SD] percentage of normal values, 9.7 +/- 3.8 percent; n = 13) than those homozygous for Type II mutation (1.2 +/- 0.5 percent, n = 16) or compound heterozygotes with Type II/III mutation (3.3 +/- 1.6 percent, n = 23), as well as significantly fewer episodes of injury-related bleeding. Each of these three groups had a similarly increased proportion of episodes of bleeding complications after surgery at sites with enhanced local fibrinolysis, such as the urinary tract, or during tooth extraction.
Type II and Type III mutations are the predominant causes of factor XI deficiency among Ashkenazi Jews. Genotypic analysis, assay for factor XI, and consideration of the type and location of surgery can be helpful in planning operations in patients with this disorder.
严重的因子 XI 缺乏症在阿什肯纳兹犹太人中相对常见，与严重的创伤相关出血有关。在 6 例因子 XI 缺乏症患者中发现了三种点突变——剪接连接异常（I 型）、Glu117→Stop（II 型）和 Phe283→Leu（III 型）。尚未对这些突变进行临床相关性研究。我们通过聚合酶链反应和限制性酶切分析，确定了这些突变的相对频率及其与因子 XI 凝血活性血浆水平和出血的关联。
在 43 例患有严重因子 XI 缺乏症的阿什肯纳兹犹太先证者中，II 型和 III 型突变的频率相似；在总共 86 个分析的等位基因中，这两种突变分别占 49%和 47%。在 40 例先证者及其 12 例患有严重因子 XI 缺乏症的亲属中，III 型突变纯合子患者的因子 XI 凝血活性水平（正常均值[±标准差]百分比，9.7±3.8%；n = 13）显著高于 II 型突变纯合子患者（1.2±0.5%，n = 十六）或 II/III 型突变复合杂合子患者（3.3±1.6%，n = 23），且创伤相关出血发作次数明显较少。这三组患者在局部纤溶增强的部位（如泌尿道）进行手术后或拔牙期间，出血并发症发作的比例均同样增加。
II 型和 III 型突变是阿什肯纳兹犹太人中因子 XI 缺乏症的主要原因。基因型分析、因子 XI 检测以及对手术类型和部位的考虑，有助于为患有这种疾病的患者制定手术计划。
