Twelve novel and two recurrent mutations in 14 Austrian families with hereditary protein C deficiency.
The molecular basis of hereditary type I and type II protein C deficiency was studied in a panel of 14 unrelated Austrian families. By direct sequencing of the nine exons and their splice junctions sequence alterations were found in one of the protein C alleles in all but one subject. In twelve subjects a single alteration was found whereas in one subject one of the protein C alleles carried two sequence abnormalities. Whenever DNA from family members was available (11 of the 14 cases) cosegregation of the protein C deficiency with the mutation was observed. In contrast to what has been found previously in a panel of Dutch patients with hereditary protein C deficiency, none of the 14 mutations occurred in more than one family. Only two of the genetic defects (157Arg-->Stop and 178Arg-->Gln) have been found previously in other geographic locations. These data confirm the large genetic heterogeneity of protein C deficiency.
Department of Hematology, University Hospital, Leiden, The Netherlands.
S R
SR
Poort
I
I
Pabinger-Fasching
C
C
Mannhalter
P H
PH
Reitsma
R M
RM
Bertina
D000595:Amino Acid Sequence; D001317:Austria; D001483:Base Sequence; D005091:Exons; D005190:Family; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011486:Protein C / Q000235:genetics*; D020151:Protein C Deficiency; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
D011486:Protein C