title: Severe prekallikrein (Fletcher factor) deficiency due to a compound heterozygosis (383Trp stop codon and Cys529Tyr).
abstract: We investigated a family with prekallikrein deficiency, using both standard coagulation tests and molecular biology techniques. The propositus was found to be a compound heterozygote for a Trp383 stop codon and a Cys529Tyr point mutation. The former mutation was located in exon 11, the latter in exon 14. The propositus inherited the first defect from his father and the second from his mother. Both parents had slightly low prekallikrein levels, but the combination of the two genetic defects produced a phenotype characterized by an extremely low prekallikrein activity and antigen. The propositus' plasma showed a progressive reduction in APTT when incubated for a long time. Conversely, plasma deficient in factor XII, factor XI or high molecular weight kininogen (HMWK) failed to show shortening of the APTT. No circulating anticoagulant was found because the patient's APTT was fully corrected by pooled nor-mal and factor XII-, factor XI- or HMWK deficient plasma. No associated abnormality was apparent in the propositus or his parents. As expected, no tendency for bleeding was noted even after tonsillectomy.
authors.affiliation: Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, University of Padua Medical School, via Ospedale Civile 105, 35128 Padua, Italy. annamaria.lombardi@unipd.it
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Lombardi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sartori
authors.forename: Laura
authors.initials: L
authors.lastname: Cabrio
authors.forename: Mariangela
authors.initials: M
authors.lastname: Fadin
authors.forename: Ezio
authors.initials: E
authors.lastname: Zanon
authors.forename: Antonio
authors.initials: A
authors.lastname: Girolami
mesh_terms: D000293:Adolescent; D001777:Blood Coagulation; D018389:Codon, Nonsense; D018388:Codon, Terminator; D004252:DNA Mutational Analysis; D005192:Family Health; D006579:Heterozygote; D006801:Humans; D007700:Kinetics; D008297:Male; D020125:Mutation, Missense; D010314:Partial Thromboplastin Time; D010641:Phenotype; D011288:Prekallikrein / Q000172:deficiency* / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D018388:Codon, Terminator; D011288:Prekallikrein