A mutation in the protein S pseudogene is linked to protein S deficiency in a thrombophilic family.

Abstract:

:Probands from 15 unrelated families with hereditary protein S deficiency type I, that is having a plasma total protein S concentration fifty percent of normal, were screened for abnormalities in their protein S genes by Southern analysis. Two probands were found to have a deviating DNA pattern with the restriction enzyme MspI. In the two patients the alteration concerned the disappearance of a MspI restriction site, CCGG, giving rise to an additional hybridizing MspI fragment. Analysis of relatives of both probands showed that in one family the mutation does not co-segregate with the phenotype of reduced plasma protein S. In the family of the other proband, however, complete linkage between the mutated gene pattern and the reduced total protein S concentration was found: 12 heterozygous relatives showed the additional MspI fragment but none of the investigated 26 normal members of the family. The mutation is shown to reside in the PS beta gene, the inactive protein S gene. The cause of type I protein S deficiency, a defect PS alpha gene has escaped detection by Southern analysis. No recombination has occurred between the PS alpha gene and the PS beta gene in 23 informative meioses. This suggests that the two protein S genes, located near the centromere of chromosome 3, are within 4 centiMorgan of each other.

journal_name

Thromb Haemost

authors

Ploos van Amstel HK,Reitsma PH,Hamulyák K,de Die-Smulders CE,Mannucci PM,Bertina RM

subject

Has Abstract

pub_date

1989-11-24 00:00:00

pages

897-901

issue

3

eissn

0340-6245

issn

2567-689X

journal_volume

62

pub_type

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