PMID- 10361121
OWN - NLM
STAT- MEDLINE
DCOM- 19990701
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 93
IP  - 12
DP  - 1999 Jun 15
TI  - Familial overexpression of beta antithrombin caused by an Asn135Thr substitution.
PG  - 4242-7
AB  - We have investigated the basis of antithrombin deficiency in an asymptomatic
      individual (and family) with borderline levels (approximately 70% antigen and
      activity) of antithrombin. Direct sequencing of amplified DNA showed a mutation
      in codon 135, AAC to ACC, predicting a heterozygous Asn135Thr substitution. This 
      substitution alters the predicted consensus sequence for glycosylation,
      Asn-X-Ser, adjacent to the heparin interaction site of antithrombin. The
      antithrombin isolated from plasma of the proband by heparin-Sepharose
      chromatography contained amounts of beta antithrombin (the very high affinity
      fraction) greatly increased (approximately 20% to 30% of total) above the trace
      levels found in normals. Expression of the residue 135 variant in both a
      cell-free system and COS-7 cells confirmed altered glycosylation arising as a
      consequence of the mutation. Wild-type and variant protein were translated and
      exported from COS-7 cells with apparently equal efficiency, in contrast to the
      reduced level of variant observed in plasma of the affected individual. This case
      represents a novel cause of antithrombin deficiency, removal of glycosylation
      concensus sequence, and highlights the potentially important role of beta
      antithrombin in regulating coagulation.
FAU - Bayston, T A
AU  - Bayston TA
AD  - Imperial College School of Medicine, London, UK.
FAU - Tripodi, A
AU  - Tripodi A
FAU - Mannucci, P M
AU  - Mannucci PM
FAU - Thompson, E
AU  - Thompson E
FAU - Ireland, H
AU  - Ireland H
FAU - Fitches, A C
AU  - Fitches AC
FAU - Hananeia, L
AU  - Hananeia L
FAU - Olds, R J
AU  - Olds RJ
FAU - Lane, D A
AU  - Lane DA
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antithrombins)
RN  - 2ZD004190S (Threonine)
RN  - 7006-34-0 (Asparagine)
RN  - 9000-94-6 (Antithrombin III)
SB  - IM
MH  - Adult
MH  - Amino Acid Sequence
MH  - Antithrombin III/chemistry/*genetics
MH  - Antithrombin III Deficiency/*genetics
MH  - Antithrombins/analysis
MH  - Asparagine/*genetics
MH  - Consensus Sequence
MH  - Female
MH  - Glycosylation
MH  - Humans
MH  - Isoelectric Focusing
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Sequence Analysis, DNA
MH  - Threonine/*genetics
MH  - Thrombosis/genetics
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - S0006-4971(20)59453-6 [pii]
PST - ppublish
SO  - Blood. 1999 Jun 15;93(12):4242-7.