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Identification of mutations in 15 Hungarian families with hereditary protein C deficiency
Author(s) -
Dávid M.,
Losonczy H.,
Sas G.,
Nagy Á.,
Kutscher G.,
Meyer M.
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2000.02324.x
Subject(s) - single strand conformation polymorphism , genetics , frameshift mutation , missense mutation , nonsense mutation , biology , exon , protein c deficiency , gene , microbiology and biotechnology , polymerase chain reaction , mutation , hereditary diseases , gene mutation , medicine , surgery , thrombosis , venous thrombosis
Hereditary protein C deficiency represents about 2–9% of inherited thrombophilias. Our aim was to elucidate the molecular basis of protein C deficiency in 25 members of 15 Hungarian families with venous thromboembolic diseases and to identify hitherto undescribed genetical defects in the protein C ( PROC ) gene. The exons of the PROC gene were screened for mutations with the combination of polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE), and/or PCR and single‐strand conformation polymorphism (SSCP) analysis. The amplified DNA fragments with aberrant migration during DGGE and SSCP were sequenced. Mutations were determined in the PROC gene in all of the examined families: one nonsense mutation, one rare frameshift deletion and nine different missense mutations, of which three were novel (1493 A→G, 35Asp→Gly; 6231 G→A, 173Gly→Glu; 8476 C→T, 254Thr→Ile). The combination of hereditary protein C deficiency with other hereditary thrombophilias was rather common. DGGE and SSCP were proved to be efficient and cost‐effective screening methods in the genetic analysis of hereditary protein C deficiency.