Genetic mutations in ten unrelated American patients with symptomatic type 1 protein C deficiency. Blood Coagul Fibrinolysis 1993 Oct;4(5):791-6
Date
10/01/1993Pubmed ID
8292730DOI
10.1097/00001721-199310000-00017Scopus ID
2-s2.0-0027520670 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
Symptomatic patients with Type 1 protein C deficiency and venous thrombosis were analysed for defects in this gene using polymerase chain reaction amplification and direct sequencing of all nine exons. Ten different heterozygous point mutations were detected in 19 patients from eleven American families. Seven represent novel mutations. Two of these were found in the TATA box or near the transcription initiation site and presumably lead to loss of transcription, and seven missense mutations were found including G103R, P168L, R169W, I201T, P279L, T298M, and C384Y. These may lead to abnormal folding or thermodynamic instability of the protein C molecule, potentially causing abnormal secretion or rapid clearance from the circulation. Two other protein C mutations, a nonsense mutation at codon Trp-145 and a deletion inducing a frameshift at codon 364 resulting in premature termination at codon 378, likely lead to unstable products. The previously published R169W mutation resulted in a Type 1 deficiency. The data show that diverse molecular defects result in similar phenotypes and emphasize that a wide variety of mutations are responsible for Type 1 protein C deficiency in the American setting of a diverse population.
Author List
Tsay W, Greengard JS, Montgomery RR, McPherson RA, Fucci JC, Koerper MA, Coughlin J, Griffin JHAuthor
Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultBase Sequence
Child
Codon
DNA
Gene Deletion
Humans
Male
Molecular Sequence Data
Mutation
Polymerase Chain Reaction
Protein C
Protein C Deficiency
TATA Box
Thrombophlebitis
Transcription, Genetic
