Karadža-Lapić Ljerka, Korošec Peter, Šilar Mira, Košnik Mitja, Cikojević Draško, Lozić Bernarda, Rijavec Matija
a General Hospital Šibenik , Šibenik , Croatia.
b University Clinic of Respiratory and Allergic Diseases Golnik , Golnik , Slovenia.
Ann Med. 2016 Nov;48(7):485-491. doi: 10.1080/07853890.2016.1185144. Epub 2016 May 17.
Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease caused by mutations in the SERPING1 gene. It can affect many regions in the body, but potentially life-threatening laryngeal oedemas are of concern.
Twenty-three subjects from two families were recruited for clinical data evaluation and molecular analysis at General Hospital Šibenik, Croatia.
Decreased levels of C1 inhibitor were detected in 12 adult patients and three young asymptomatic persons. The same novel deletion of two nucleotides on exon 3 (c.74_75delAT) was identified in all of them. A history of laryngeal oedema was present in 10 patients (83%), and all patients reported laryngeal attacks at least once a year. The delay in diagnosis decreased noticeably from the first to the last generation.
We identified a novel causative mutation in SERPING1 in several affected members of two apparently unrelated families with a high frequency of laryngeal oedema. Molecular analysis of large C1-INH-HAE families will provide new insights on the genotype-phenotype relationship. Key messages Hereditary angioedema due to C1 inhibitor deficiency is a rare autosomal dominant disease caused by mutations in the SERPING1 gene, and laryngeal oedema is of concern because it can cause death by asphyxiation. A novel causative mutation in SERPING1, a deletion of two nucleotides on exon 3 (c.74_75delAT), was identified in several affected members of two apparently unrelated families with a high frequency of laryngeal oedema. Molecular analysis of large C1-INH-HAE families will provide new insights on the genotype-phenotype relationship because it appears that the mutation type may affect disease severity.
C1 抑制物缺乏所致遗传性血管性水肿（C1-INH-HAE）是一种由 SERPING1 基因突变引起的罕见常染色体显性疾病。它可累及身体多个部位，但潜在危及生命的喉水肿令人担忧。
招募了来自两个家族的 23 名受试者，在克罗地亚希贝尼克总医院进行临床资料评估和分子分析。
在 12 名成年患者和 3 名年轻无症状者中检测到 C1 抑制物水平降低。在所有这些人中均鉴定出第 3 外显子上两个核苷酸的相同新发缺失（c.74_75delAT）。10 名患者（83%）有喉水肿病史，所有患者均报告每年至少发生一次喉部发作。从第一代到最后一代，诊断延迟明显缩短。
我们在两个明显无关的家族中，在多个受累成员中鉴定出 SERPING1 基因的一种新的致病突变，这些家族中喉水肿发生率很高。对大型 C1-INH-HAE 家族进行分子分析将为基因型-表型关系提供新的见解。关键信息 C1 抑制物缺乏所致遗传性血管性水肿是一种由 SERPING1 基因突变引起的罕见常染色体显性疾病，喉水肿令人担忧，因为它可导致窒息死亡。在两个明显无关的家族中，在多个受累成员中鉴定出 SERPING1 基因的一种新的致病突变，即第 3 外显子上两个核苷酸的缺失（c.74_75delAT），这些家族中喉水肿发生率很高。对大型 C1-INH-HAE 家族进行分子分析将为基因型-表型关系提供新的见解，因为似乎突变类型可能影响疾病严重程度。
