Department of Dermatology, Johannes Gutenberg University, Mainz, Germany.
Clin Immunol. 2011 Oct;141(1):31-5. doi: 10.1016/j.clim.2011.07.002. Epub 2011 Jul 30.
In hereditary angioedema with normal C1-inhibitor two different missense mutations of codon p.Thr328* in the coagulation factor 12 gene have been reported in some families. In this study a novel factor 12 gene mutation, the deletion of 72 base pairs (bp) (c.971_1018+24del72*), was identified in a family of Turkish origin, in two sisters with recurrent skin swellings and abdominal pain attacks and in their symptom-free father. This deletion caused a loss of 48 bp of exon 9 (coding amino acids 324* to 340*) in addition to 24 bp of intron 9, including the authentic donor splice site of exon 9. The large deletion of 72 bp was located in the same F12 gene region as the missense mutations p.Thr328Lys* and p.Thr328Arg* reported previously. Our findings confirm the association between F12 gene mutations modifying the proline-rich region of the FXII protein and hereditary angioedema with normal C1-inhibitor.
在正常 C1 抑制剂的遗传性血管水肿中，已经在一些家族中报告了凝血因子 12 基因中密码子 p.Thr328的两个不同错义突变。在这项研究中，在一个具有土耳其血统的家族中，发现了一个新的因子 12 基因突变，即 72 个碱基对（bp）的缺失（c.971_1018+24del72），该家族中有两名反复发作皮肤肿胀和腹痛的姐妹，以及无症状的父亲。该缺失导致 9 号外显子（编码氨基酸 324至 340）的 48 个 bp 丢失，以及 9 号内含子的 24 个 bp 丢失，包括 9 号外显子的真实供体位点。72 bp 的大片段缺失位于与先前报道的错义突变 p.Thr328Lys和 p.Thr328Arg相同的 F12 基因区域。我们的发现证实了 FXII 蛋白脯氨酸丰富区域的 F12 基因突变与正常 C1 抑制剂的遗传性血管水肿之间的关联。
