The prevalence of, and molecular defects underlying, inherited protein S deficiency in the general population

Beauchamp, N. J., Dykes, A. C., Parikh, N., Tait, R. C. and Daly, M. E. (2004) The prevalence of, and molecular defects underlying, inherited protein S deficiency in the general population. British Journal of Haematology, 125(5), pp. 647-654. (doi: 10.1111/j.1365-2141.2004.04961.x) (PMID:15147381)

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Abstract

The molecular basis of protein S (PS) deficiency was investigated in seven of eight donors identified with persistently low plasma PS levels from a survey of PS levels in 3788 Scottish blood donors. PROS1 gene analysis identified at least one defect in six donors. Five were heterozygous for the Heerlen polymorphism predicting a Ser460Pro substitution. Haplotype analysis revealed the possibility that this allele was inherited with the same haplotype in four of the five donors, suggesting a founder effect for the Heerlen allele in this population. One Heerlen allele carrier was also heterozygous for a 3 bp deletion 68–72 bp upstream of exon 2. Platelet PROS1 transcript analysis showed no reduction in mRNA expression from the affected allele in this donor. A T to G transversion 3 bp upstream of exon 12 was identified in one donor, which is predicted to reduce the efficiency of PS mRNA splicing. However, PROS1 transcript analysis showed no evidence of exon skipping or cryptic splicing. No PROS1 gene defect was detected in the remaining donor. This genetic information enabled us to refine our estimate of the prevalence of heritable PS deficiency in the Scottish population to between 0·16% and 0·21%, predominantly resulting from the presence of the Heerlen allele.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tait, Dr Robert
Authors: Beauchamp, N. J., Dykes, A. C., Parikh, N., Tait, R. C., and Daly, M. E.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:British Journal of Haematology
Publisher:Blackwell Publishing
ISSN:0007-1048
ISSN (Online):1365-2141
Published Online:27 April 2004

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