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Thromb Haemost 1995; 74(05): 1215-1220
DOI: 10.1055/s-0038-1649914
Original Article
Clinical Studies
Schattauer GmbH Stuttgart

Severe Type I Protein C Deficiency in a Compound Heterozygote for Y124C and Q132X Mutations in Exon 6 of the PROC Gene

José Manuel Soria
1   The Molecular Genetics Department, IRO, Cancer Research Institute Hospital Duran I Reynals, Barcelona
,
Marta Morell
1   The Molecular Genetics Department, IRO, Cancer Research Institute Hospital Duran I Reynals, Barcelona
,
Carmen Jimeénez-Astorga
2   The Haematology Service, Hospital La Fe, Valencia, Spain
,
Xavier Estivill
1   The Molecular Genetics Department, IRO, Cancer Research Institute Hospital Duran I Reynals, Barcelona
,
Nuúria Sala
1   The Molecular Genetics Department, IRO, Cancer Research Institute Hospital Duran I Reynals, Barcelona
› Author Affiliations
Further Information

Publication History

Received 13 January 1995

Accepted after resubmission 14 July 1995

Publication Date:
10 July 2018 (online)

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Summary

We report the genetic abnormalities in the protein C genes of a Spanish child with neonatal purpura fulminans and disseminated intravascular coagulation, associated with undetectable protein C levels. Direct sequencing of the nine protein C gene exons and their splice junctions indicated that the proband is a compound heterozygote with two mutant protein C gene alleles, Y124C and Q132X, that do not express protein C in plasma. The Y124C mutation was inherited from the mother and is due to a novel A to G transition at nucleotide 3416, which results in the substitution of cysteine for tyrosine 124, a highly conserved amino acid in EGF-like domains. The paternal inherited mutation (Q132X) is a C to T transition at nucleotide 3439, which replaces glutamine 132 with a Stop codon signal. This mutation, if expressed, should result in the synthesis of a truncated protein of 131 amino acids. Y124C or Q132X are present in the heterozygous state in the asymptomatic parents and siblings of the proband, all of which have half the normal plasma levels of protein C. Q123X has also been identified in families where type I PC deficiency is inherited as a clinically dominant trait. Therefore, the presence of the same mutation in a family showing a clinically recessive pattern of inheritance indicates that other factors, apart from the type of protein C gene mutation, are responsible for the clinical expression of protein C deficiency.

 

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