1993 Fiscal Year Final Research Report Summary
Studies on the genetic analysis of a patient with protein C deficien
| Project/Area Number |
04671433
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory medicine
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| Research Institution | Mie University |
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Principal Investigator |
IDO Masaru Mie University, Faculty of Medicine Lecturer, 医学部, 講師 (90167263)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Koji Mie University, Faculty of Medicine Professor, 医学部, 教授 (70077808)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Protein C deficiency / Gene analysis / Prenatal diagnocis / Congenital anomaly / Thrombosis |
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| Research Abstract |
We report genetic abnormalities of protein C gene in a male infant who developed neonatal purpura fulminans. DNA-sequence analysis of all cxons in protein C gene in this family revealed two mutations the first abnormality, derived from the mother, was a deletion of one of four consccutive g at nucleotide number 10758 in exon IX which would result in a frame shift mutation and com ; letely change amino acid sequence from Gly381 in the carboxyl-terminal region of protein C.The second abnormality, derived from the father, was a single nucleotide mutation from G to A in the codon (GAG to AAG) at nucleotide number 2977 in exon III, which would result in a substitution of Lys for gamma-carboxyglutamic acid (Gla) 26. This change would be responsible for the reduced immunological protein C levels of the patient and the father, estimated by a monoclonal antibody which recognizes the Gla-domain in a Ca^<2+>-dependent manner (3.8% and 57%, respectively). Partially purified abnormal protein C from the father's plasma showed a normal amidolytic activity and a change in the electrophoretic mobility. We detected the above mutations in his family members using two methods ; one was a creation of new restriction enzyme sites using mutagenic primers and the other was single nucleotide primer extension. Both methods are rapid and useful for the diagnosis of prenatal protein C abnormalities.
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