Compound heterozygous protein C deficiency resulting in the presence of
only the beta-form of protein C in plasma
P Simioni, M Kalafatis, DS Millar, SC Henderson, S Luni, DN Cooper and A Girolami
Institute of Medical Semeiotics, University-Hospital of Padua Medical
School, Italy.
About 30% of human plasma protein C (PC) is of lower molecular weight than
the predominant alpha-form. The minor beta-form arises as a consequence of
the lack of glycosylation at Asn329. Although the functional role of Asn329
has been investigated by in vitro mutagenesis, until now no naturally
occurring mutations have been reported at this site. We describe here the
case of two identical twin sisters compound heterozygous for two novel PC
mutations: Cys78-->Stop inherited from the maternal side and
Asn329-->Thr inherited from the paternal side, associated with the
presence of only the beta-form of PC in plasma. The Cys78-->Stop
substitution is predicted to abolish PC synthesis from one allele, whereas
the Asn329-->Thr substitution results in the reduced synthesis of a beta
PC variant with decreased functional activity. PCN329T from the two
monovular twin sisters was purified and its active form APCN329T was
assessed for its ability to inactivate factor Va. Whereas no differences
were observed between the activation rates of normal PC and PCN329T,
APCN329T inactivated human factor Va with a rate slower than the normal
APC. This is the first report of a PC defect involving glycosylation of the
molecule. This defect results in the presence of only the beta-form of PC
in human plasma and is responsible for the reduced anticoagulant activity
observed.
Volume 88,
Issue 6,
pp. 2101-2108,
09/15/1996
Copyright © 1996 by The American Society of Hematology
