PMID- 10233432
OWN - NLM
STAT- MEDLINE
DCOM- 19990624
LR  - 20131121
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 105
IP  - 2
DP  - 1999 May
TI  - Homozygous Cys542-->Arg substitution in GPIIIa in a Swiss patient with type I
      Glanzmann's thrombasthenia.
PG  - 523-31
AB  - Glanzmann's thrombasthenia (GT) arises from a qualitative or quantitative defect 
      in the GPIIb-IIIa complex (integrin alphaIIbbeta3), the mediator of platelet
      aggregation. We describe a patient in whom clinical and laboratory findings
      typical of type I GT were found together with a second pathology involving
      neurological and other complications symptomatic of tuberous sclerosis. Analysis 
      of platelet proteins by Western blotting revealed trace amounts of normally
      migrating GPIIb and equally small amounts of GPIIIa of slightly slower than
      normal migration. Flow cytometry confirmed a much decreased binding to platelets 
      of monoclonal antibodies to GPIIb, GPIIIa or GPIIb-IIIa, and an antibody to the
      alphav subunit also showed decreased binding. Nonradioactive PCR single-strand
      conformation polymorphism analysis followed by direct sequencing of PCR-amplified
      DNA fragments showed a homozygous point mutation (T to C) at nucleotide 1722 of
      GPIIIa cDNA and which led to a Cys542-->Arg substitution in the GPIIIa protein.
      The mutation gave rise to a HinP1 I restriction site in exon 11 of the GPIIIa
      gene and allele-specific restriction enzyme analysis of family members confirmed 
      that a single mutated allele was inherited from each parent. This amino acid
      substitution presumably changes the capacity for disulphide bond formation within
      the cysteine-rich core region of GPIIIa and its study will provide new
      information on GPIIb-IIIa and alphavbeta3 structure and biosynthesis.
FAU - Ruan, J
AU  - Ruan J
AD  - UMR 5533 CNRS, Hopital Cardiologique, Pessac, France.
FAU - Schmugge, M
AU  - Schmugge M
FAU - Clemetson, K J
AU  - Clemetson KJ
FAU - Cazes, E
AU  - Cazes E
FAU - Combrie, R
AU  - Combrie R
FAU - Bourre, F
AU  - Bourre F
FAU - Nurden, A T
AU  - Nurden AT
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 94ZLA3W45F (Arginine)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Amino Acid Substitution/*genetics
MH  - Arginine/genetics
MH  - Blotting, Western
MH  - Child, Preschool
MH  - Cysteine/genetics
MH  - Female
MH  - Flow Cytometry
MH  - Homozygote
MH  - Humans
MH  - Pedigree
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/*genetics
MH  - Polymorphism, Single-Stranded Conformational
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Thrombasthenia/*genetics
EDAT- 1999/05/08 00:00
MHDA- 1999/05/08 00:01
CRDT- 1999/05/08 00:00
PHST- 1999/05/08 00:00 [pubmed]
PHST- 1999/05/08 00:01 [medline]
PHST- 1999/05/08 00:00 [entrez]
PST - ppublish
SO  - Br J Haematol. 1999 May;105(2):523-31.