Antithrombin-Gly 424 Arg: a novel point mutation responsible for type 1
antithrombin deficiency and neonatal thrombosis
K Jochmans, W Lissens, R Vervoort, S Peeters, M De Waele and I Liebaers
Department of Hematology, Academic Hospital of the Free University of
Brussels, Belgium.
Inherited type 1 antithrombin (AT) III deficiency is characterized by a
decrease of immunoreactive and functional protein levels to about 50%. The
disorder is associated with a significantly increased risk of
thromboembolism. We have investigated the molecular basis of type 1 AT
deficiency in a Belgian family. The diagnosis of the disease was primarily
made in a newborn girl with unusually severe thrombotic complications.
Using the polymerase chain reaction and single-strand conformation
polymorphism analysis, followed by direct sequencing of AT gene fragments,
we identified a novel point mutation in exon 6. We detected a G to C
substitution in the first position of codon 424 leading to a glycine to
arginine substitution. The modification at this highly conserved position
in the serine protease inhibitor gene family probably leads to an unstable
mutant-gene product. The mutation creates a unique restriction site for the
enzyme Hha I in exon 6. This change permitted a rapid and accurate
screening of the kindred with identification of the molecular defect in
five other family members.
Volume 83,
Issue 1,
pp. 146-151,
01/01/1994
Copyright © 1994 by The American Society of Hematology
