期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1990
卷号：87
期号：17
页码：6786-6790
DOI：10.1073/pnas.87.17.6786
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Hereditary angioneurotic edema is inherited as an autosomal dominant disorder and is characterized by potentially life-threatening episodic angioedema. In type II hereditary angioneurotic edema, a dysfunctional C1 inhibitor molecule is present together with low levels of normal C1 inhibitor. About 70% of these dysfunctional proteins result from reactive center (Arg-444) mutations. We describe the deletion of nucleotides encoding Lys-251 (AAG) in C1 inhibitor Ta, the dysfunctional C1 inhibitor from a family with type II hereditary angioneurotic edema. DNA sequence analysis was derived from clones obtained through polymerase chain reaction amplification of blood monocyte C1 inhibitor mRNA. As expected, clones with both normal and abnormal sequence were isolated. The deletion was verified by protein sequence analysis. These data, together with biochemical analysis of the protein and cell-free translation studies, suggest that this deletion, by altering the normal amino acid sequence from Asn-Lys-Ile-Ser to Asn-Ile-Ser, creates a new glycosylation site. The additional carbohydrate accounts for the larger size on SDS/PAGE and very likely interferes with protein function.
