Abstract |
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.
|
Authors | Yelena Krijanovski, Valerie Proulle, Fakhri Mahdi, Marie Dreyfus, Werner Müller-Esterl, Alvin H Schmaier |
Journal | Blood
(Blood)
Vol. 101
Issue 11
Pg. 4430-6
(Jun 01 2003)
ISSN: 0006-4971 [Print] United States |
PMID | 12576314
(Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Codon, Nonsense
- Kininogen, High-Molecular-Weight
- Kininogens
|
Topics |
- Child
- Codon, Nonsense
- Exons
- Family Health
- Frameshift Mutation
- Humans
- Immunoblotting
- Introns
- Kininogen, High-Molecular-Weight
(biosynthesis, deficiency, genetics)
- Kininogens
(biosynthesis, genetics, metabolism)
- Male
- Protein Structure, Tertiary
- Thrombosis
(blood, genetics)
|