TY - JOUR
T1 - A mutation in the protein S pseudogene is linked to protein S deficiency in a thrombophilic family
AU - Ploos Van Amstel, H. K.
AU - Reitsma, P. H.
AU - Hamulyak, K.
AU - De Die-Smulders, C. E M
AU - Mannucci, P. M.
AU - Bertina, R. M.
PY - 1989
Y1 - 1989
N2 - 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 PSβ gene, the inactive protein S gene. The cause of type I protein S deficiency, a defect PSα gene has escaped detection by Southern analysis. No recombination has occurred between the PSα gene and the PSβ 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.
AB - 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 PSβ gene, the inactive protein S gene. The cause of type I protein S deficiency, a defect PSα gene has escaped detection by Southern analysis. No recombination has occurred between the PSα gene and the PSβ 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.
KW - Protein S
KW - Pseudogene
KW - Thrombophilia
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M3 - Article
C2 - 2531940
AN - SCOPUS:0024307180
VL - 62
SP - 897
EP - 901
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
SN - 0340-6245
IS - 3
ER -