Characterization of molecular defects of Fitzgerald trait and another novel high-molecular-weight kininogen-deficient patient: insights into structural requirements for kininogen expression
| Autor: | Marie Dreyfus, Valérie Proulle, Fakhri Mahdi, Alvin H. Schmaier, Yelena Krijanovski, Werner Müller-Esterl |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Kininogen High-Molecular-Weight High-molecular-weight kininogen Immunoblotting Immunology Biology medicine.disease_cause Biochemistry Epitope Frameshift mutation Exon Complementary DNA medicine Humans Child Frameshift Mutation Family Health Genetics chemistry.chemical_classification Kininogen Mutation Kininogens Thrombosis Exons Cell Biology Hematology Molecular biology Introns Protein Structure Tertiary Amino acid chemistry Codon Nonsense |
| Zdroj: | Blood. 101:4430-4436 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2002-11-3329 |
| Popis: | A 6-year-old male with vertebral-basilar artery thrombosis was recognized to have high-molecular-weight kininogen (HK) deficiency. The propositus had no HK procoagulant activity and antigen (< 1%). Using monoclonal antibodies (Mabs) to kininogen domain 3, the propositus, family members, and Fitzgerald plasma were determined to have detectable low-molecular-weight kininogen. Mabs to HK domains 5 and 6 do not detect HK antigen in the propositus' plasma. The propositus has a single base pair (bp) deletion in cDNA position 1492 of exon 10 affecting amino acid 480 of the mature protein and resulting in a frameshift and a premature stop codon at position 1597 (amino acid 532). Unexpectedly, Mabs to the heavy chain and domain 5 of HK detect a 92-kDa form of HK in Fitzgerald plasma, the first HK-deficient plasma. The 92-kDa Fitzgerald HK has amino acid residues through 502, corresponding to domains 1 through 5, but lacks epitopes of domain 6 (positions 543 to 595). Fitzgerald DNA has a normal exon 10, but a 17-bp mutation in intron 9. These combined results indicate that mutations in the kininogen gene may differentially affect biosynthesis, processing, and/or secretion of HK. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|