PMID- 10089893
OWN - NLM
STAT- MEDLINE
DCOM- 19990419
LR  - 20190909
IS  - 0902-4441 (Print)
IS  - 0902-4441 (Linking)
VI  - 62
IP  - 3
DP  - 1999 Mar
TI  - Molecular characterization of two mutations in platelet glycoprotein (GP) Ib
      alpha in two Finnish Bernard-Soulier syndrome families.
PG  - 160-8
AB  - Bernard-Soulier syndrome (BSS) is a rare hereditary bleeding disorder and
      macrothrombocytopenia which is caused by a defect in the platelet glycoprotein
      Ib/IX/V (GP Ib/IX/V) complex, the receptor for von Willebrand factor and
      thrombin. Here we report the molecular basis of the classical form of BSS in two 
      unrelated Finnish patients, both with a life-long history of severe bleeding.
      Flow cytometry and immunoblotting showed no expression of GP Ib/IX, GP Ib alpha, 
      GP Ib beta or GP IX (less than 10%) in the patients' platelets. No expression of 
      GP V (< 10%) was observed in propositus 1, but a residual amount was found in
      propositus 2 (24%). DNA sequencing analysis revealed that propositus 1 was
      compound heterozygous for a two-base-pair deletion at Tyr505(TAT) and a point
      mutation Leu129(CTC)Pro(CCC) in the GP Ib alpha gene. Propositus 2 was homozygous
      for the Tyr505(TAT) deletion. The nine relatives who were heterozygous for either
      of the mutations also had low levels of GP Ib alpha (74-90%). Hence,
      Bernard-Soulier patients homozygous or compound heterozygous for Tyr505(TAT) are 
      severely affected. Interestingly, both mutations have independently been found in
      three other families in previous reports, suggesting their ancient age or
      mutational 'hot spot'.
FAU - Koskela, S
AU  - Koskela S
AD  - Finnish Red Cross Blood Transfusion Service, Helsinki, Finland.
FAU - Partanen, J
AU  - Partanen J
FAU - Salmi, T T
AU  - Salmi TT
FAU - Kekomaki, R
AU  - Kekomaki R
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 0 (Platelet Glycoprotein GPIb-IX Complex)
SB  - IM
MH  - Bernard-Soulier Syndrome/epidemiology/*genetics
MH  - Child
MH  - DNA Mutational Analysis
MH  - Female
MH  - Finland/epidemiology
MH  - Flow Cytometry
MH  - Genotype
MH  - Humans
MH  - Immunoblotting
MH  - Infant, Newborn
MH  - Male
MH  - Pedigree
MH  - Platelet Glycoprotein GPIb-IX Complex/*genetics
MH  - *Point Mutation
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Restriction Fragment Length
MH  - Polymorphism, Single-Stranded Conformational
MH  - *Sequence Deletion
EDAT- 1999/03/25 00:00
MHDA- 1999/03/25 00:01
CRDT- 1999/03/25 00:00
PHST- 1999/03/25 00:00 [pubmed]
PHST- 1999/03/25 00:01 [medline]
PHST- 1999/03/25 00:00 [entrez]
AID - 10.1111/j.1600-0609.1999.tb01739.x [doi]
PST - ppublish
SO  - Eur J Haematol. 1999 Mar;62(3):160-8. doi: 10.1111/j.1600-0609.1999.tb01739.x.