Department of Dermatology, Johannes Gutenberg University, Mainz, Germany.
University Medicine, Ernst Moritz Arndt University, Greifswald, Germany.
Allergy. 2015 Aug;70(8):1004-12. doi: 10.1111/all.12648. Epub 2015 May 22.
Hereditary angioedema with normal C1-INH may be linked to specific mutations in the coagulation factor 12 (FXII) gene (HAE-FXII) or mutations in genes that are still unknown (HAE-unknown). To assess the differences in transmission and inheritance, clinical features, and laboratory parameters between patients with HAE-FXII and HAE-unknown.
Sixty-nine patients with HAE-FXII from 23 unrelated families and 196 patients with HAE-unknown from 65 unrelated families were studied.
Both HAE-FXII and HAE-unknown are inherited as autosomal-dominant traits with incomplete penetrance. The male to female ratio was 1 : 68 in HAE-FXII and 1 : 6.3 in HAE-unknown. The maternal to paternal transmission ratio was 35 : 14 for HAE-FXII and 109 : 12 for HAE-unknown. Mean age at onset of clinical symptoms was 20.3 years in patients with HAE-FXII and 29.6 years in patients with HAE-unknown. The incidence of asphyxiation due to angioedema was similar for HAE-FXII and HAE-unknown. Oral contraceptives and pregnancies had a significantly higher impact on HAE-FXII than on HAE-unknown. Slightly decreased C1-INH activity and C4 concentration were observed in more patients with HAE-FXII than HAE-unknown. Tests for FXI and FXII activity, plasminogen activator inhibitor 1, and activated partial thromboplastin time showed variability but no significant differences between the groups. No abnormalities were found for C1-INH protein, C1q, alpha2-macroglobulin, antithrombin III, and angiotensin-converting enzyme. In families with HAE-FXII, the number of female offspring with F12 mutations was significantly increased and that of male offspring was significantly decreased.
HAE-FXII and HAE-unknown differ in various respects, including gender distribution, genetics, symptoms, and estrogen impact.
具有正常 C1-INH 的遗传性血管性水肿可能与凝血因子 12（FXII）基因（HAE-FXII）的特定突变或仍未知的基因突变有关（HAE-未知）。评估 HAE-FXII 和 HAE-未知患者在传播和遗传、临床特征和实验室参数方面的差异。
研究了 23 个无关家族的 69 名 HAE-FXII 患者和 65 个无关家族的 196 名 HAE-未知患者。
HAE-FXII 和 HAE-未知均为不完全外显率的常染色体显性遗传特征。HAE-FXII 的男女比例为 1:68，HAE-未知为 1:6.3。HAE-FXII 的母系到父系的传递比例为 35:14，HAE-未知为 109:12。HAE-FXII 患者的临床症状起始年龄为 20.3 岁，HAE-未知患者为 29.6 岁。HAE-FXII 和 HAE-未知 的血管性水肿窒息发生率相似。口服避孕药和妊娠对 HAE-FXII 的影响明显大于 HAE-未知。与 HAE-未知相比，更多的 HAE-FXII 患者观察到 C1-INH 活性和 C4 浓度略有降低。FXI 和 FXII 活性、纤溶酶原激活物抑制剂 1 和活化部分凝血活酶时间的检测结果存在差异，但组间无显著差异。未发现 C1-INH 蛋白、C1q、α2-巨球蛋白、抗凝血酶 III 和血管紧张素转换酶异常。在 HAE-FXII 家族中，F12 突变女性后代的数量显著增加，男性后代的数量显著减少。
HAE-FXII 和 HAE-未知在性别分布、遗传学、症状和雌激素影响等方面存在差异。
