title: Compound heterozygosity for two novel missense mutations in the prothrombin gene in a patient with a severe bleeding tendency.
abstract: The abnormal prothrombin gene of an Italian patient with a severe bleeding tendency and hypoprothrombinemia was selected for study and compared with the prothrombin genes of healthy controls. All the coding and their flanking regions and the 5'- and 3'-UT regions of the prothrombin gene were screened by analyzing the nucleotide sequence of the corresponding PCR products. The patient was found to be heterozygous for two novel point mutations: one at nucleotide 4251 in exon 6, which changes the codon for cysteine-138 (TGC) in the kringle 1 domain to that for tyrosine (TAC), and one at nucleotide 8812 in exon 10, which results in the replacement of tryptophan-357 (TGG) by cysteine (TGT) in the catalytic domain. Her mother was heterozygous for the Cys-138 Tyr mutation and her father heterozygous for the Trp-357 Cys mutation. Several other sequence variations were identified in the prothrombin genes from control individuals. Only the variations at nucleotide 4203 and 10253 could be established as polymorphisms.
authors.affiliation: Department of Hematology, University Hospital Leiden, The Netherlands.
authors.forename: S R
authors.initials: SR
authors.lastname: Poort
authors.forename: R
authors.initials: R
authors.lastname: Landolfi
authors.forename: R M
authors.initials: RM
authors.lastname: Bertina
mesh_terms: D001779:Blood Coagulation Factors / Q000235:genetics; D003545:Cysteine / Q000737:chemistry; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006470:Hemorrhage / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007020:Hypoprothrombinemias / Q000235:genetics*; D007231:Infant, Newborn; D017354:Point Mutation; D011516:Prothrombin / Q000235:genetics*; D012016:Reference Values; D017422:Sequence Analysis, DNA; D014364:Tryptophan / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry
chemical_list: D001779:Blood Coagulation Factors; D014443:Tyrosine; D014364:Tryptophan; D011516:Prothrombin; D003545:Cysteine