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Thromb Haemost 1994; 72(01): 065-069
DOI: 10.1055/s-0038-1648812
Original Article
Schattauer GmbH Stuttgart

Severe Homozygous Protein C Deficiency: Identification of a Splice Site Missense Mutation (184, Q → H) in Exon 7 of the Protein C Gene

J M Soria
1   The Molecular Genetics Department IRO Cancer Research Institute, Hospital Duran i Reynals, Barcelona, Spain
,
D Brito
2   Haematology Service, Hospital Regional Carlos Haya, Màlaga, Spain
,
J Barceló
2   Haematology Service, Hospital Regional Carlos Haya, Màlaga, Spain
,
J Fontcuberta
3   Haemostasis and Thrombosis Unit, Haematology Service, Hospital de Sant Pau, Barcelona, Spain
,
L Botero
2   Haematology Service, Hospital Regional Carlos Haya, Màlaga, Spain
,
J Maldonado
2   Haematology Service, Hospital Regional Carlos Haya, Màlaga, Spain
,
X Estivill
1   The Molecular Genetics Department IRO Cancer Research Institute, Hospital Duran i Reynals, Barcelona, Spain
,
N Sala
1   The Molecular Genetics Department IRO Cancer Research Institute, Hospital Duran i Reynals, Barcelona, Spain
› Author Affiliations
Further Information

Publication History

Received 22 October 1993

Accepted after resubmission 10 March 1994

Publication Date:
12 July 2018 (online)

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Summary

Single strand conformation polymorphism (SSCP) analysis of exon 7 of the protein C gene has identified a novel splice site missense mutation (184, Q → H), in a newborn child with purpura fulminans and undetectable protein C levels. The mutation, seen in the homozygous state in the child and in the heterozygous state in her mother, was characterized and found to be a G to C nucleotide substitution at the -1 position of the donor splice site of intron 7 of the protein C gene, which changes histidine 184 for glutamine (184, Q → H). According to analysis of the normal and mutated sequences, this mutation should also abolish the function of the donor splice site of intron 7 of the protein C gene. Since such a mutation is compatible with the absence of gene product in plasma and since DNA sequencing of all protein C gene exons in this patient did not reveal any other mutation, we postulate that mutation 184, Q → H results in the absence of protein C gene product in plasma, which could be the cause of the severe phenotype observed in this patient.

 

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