title: Homozygous type I protein C deficiency in two unrelated families exhibiting thrombophilia related to Ala136-->Pro or Arg286-->His mutations.
abstract: Separate single nucleotide mutations have been identified in two unrelated homozygous type I protein C deficient individuals suffering from thrombophilia. Each mutation, initially established by direct DNA sequencing of polymerase chain reaction amplification products, results in an amino acid substitution. The first mutation (PCClamart) results in an Ala136 to Pro substitution in the protein's second epidermal growth factor-like domain. The second mutation (PCMünchen) results in an Arg286 to His substitution in the serine protease domain. Comparison of the location of these two mutations and the relative conservation of the two regions in homologous vitamin K-dependent plasma proteins is consistent with the difference in severity of protein C deficiency and disease in the two individuals. Both mutations result in the abolition of a naturally occurring restriction endonuclease site, thereby allowing independent confirmation of the mutations and rapid and unambiguous genetic analysis of protein C deficiency in family members. In both families, the genetic analysis has proven useful in cases where an assignment of the protein C status based upon clinical laboratory measurements was either ambiguous or incorrect.
authors.affiliation: Department of Biochemistry, School of Medicine, University of Vermont, Burlington.
authors.forename: G L
authors.initials: GL
authors.lastname: Long
authors.forename: J A
authors.initials: JA
authors.lastname: Tomczak
authors.forename: I R
authors.initials: IR
authors.lastname: Rainville
authors.forename: M
authors.initials: M
authors.lastname: Dreyfus
authors.forename: W
authors.initials: W
authors.lastname: Schramm
authors.forename: H P
authors.initials: HP
authors.lastname: Schwarz
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004211:Disseminated Intravascular Coagulation / Q000151:congenital / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011486:Protein C / Q000235:genetics; D020151:Protein C Deficiency; D011693:Purpura / Q000151:congenital / Q000235:genetics; D013924:Thrombophlebitis / Q000235:genetics; D013927:Thrombosis / Q000235:genetics*
chemical_list: D011486:Protein C