Three novel mutations in five unrelated subjects with hereditary protein S deficiency type I

A panel of eight unrelated subjects with inherited type I protein S deficiency was screened for mutations in the PROS1 gene. In five subjects an abnormality was found but mutations were not detected in the remaining three subjects. Two subjects shared a G-->A transition at position +5 of the dono...

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Bibliographic Details
Published in:The Journal of clinical investigation 1994-02, Vol.93 (2), p.486-492
Main Authors: REITSMA, P. H, VAN AMSTEL, H. K. P, BERTINA, R. M
Format: Article
Language:English
Subjects:
Alleles
Base Sequence
Biological and medical sciences
Blood Platelets - metabolism
coagulation
deficiency
DNA Primers
Exons
Female
genes
Hematologic and hematopoietic diseases
Humans
Male
man
Medical sciences
Molecular Sequence Data
mutation
Pedigree
Platelet diseases and coagulopathies
Point Mutation
Polymerase Chain Reaction
PROS1 gene
protein S
Protein S - genetics
Protein S Deficiency
RNA, Messenger - biosynthesis
RNA, Messenger - blood
splicing
Transcription, Genetic
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Summary:A panel of eight unrelated subjects with inherited type I protein S deficiency was screened for mutations in the PROS1 gene. In five subjects an abnormality was found but mutations were not detected in the remaining three subjects. Two subjects shared a G-->A transition at position +5 of the donor splice site consensus sequence of intron 10. Also in two subjects an A-->T transversion was detected in the stopcodon of the PROS1 gene; this transversion predicts a protein S molecule that is extended by 14 amino acids. The fifth subject was found to possess two sequence abnormalities. One allele carried a G-->A transition near the donor splice junction of intron 2, but this abnormality is probably neutral, since it was inherited from the parent with normal protein S antigen levels. In the other allele a single T insertion in codon -25 was found. Analysis of platelet RNA showed that only the mRNA with the A-->T mutation in the stopcodon is present in amounts comparable to wildtype RNA. mRNA from the alleles with the other two mutations was either undetectable or present in greatly reduced amounts. The latter indicates that a mRNA based approach is not feasible for the genetic analysis of protein S deficiency type I.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI116997