Novel mutation (E113X) of antithrombin III gene (AT3) in a woman with gestational recurrent thrombosis.
A 35-year-old Japanese woman with a low level (42-54%) of blood antithrombin (AT) III, experienced two induced abortions due to deep venous thrombosis at 8 weeks of gestation (GW) and cerebral thrombosis at 10 GW. The present pregnancy was successfully managed with intravenous administration of AT III (6,000-8,000 U/wk). Analysis of polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) for exons 3A and 4 of the AT III gene (AT3) using her DNA revealed extra expansion bands with altered migration. The DNA sequencing demonstrated novel mutations in exon 3A of AT3: a G to T substitution at nucleotide position 5333 in codon GAG for Glu 113, causing a stop codon (E113X), and an A to T substitution at position 5338 in codon AAA for Lys 114, forming Asn (K114N). These novel mutations, especially E113X, in AT3 may be related to recurrent thrombosis in the pregnancy.
Yamada
H
H
Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Sapporo, Japan. yhideto@med.hokudai.ac.jp
Hoshi
N
N
Kato
E H
EH
Ebina
Y
Y
Kishida
T
T
Sagawa
T
T
Matsuno
K
K
Fujimoto
S
S
D000028:Abortion, Induced; D000328:Adult; D000990:Antithrombin III / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular; D012008:Recurrence; D013927:Thrombosis / Q000235:genetics*
D000990:Antithrombin III