PMID- 11222377
OWN - NLM
STAT- MEDLINE
DCOM- 20010419
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 97
IP  - 5
DP  - 2001 Mar 1
TI  - Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of 
      heterozygous Bernard-Soulier syndrome.
PG  - 1330-5
AB  - A form of autosomal dominant macrothrombocytopenia is characterized by mild or no 
      clinical symptoms, normal platelet function, and normal megakaryocyte count. 
      Because this condition has so far received little attention, patients are subject 
      to misdiagnosis and inappropriate therapy. To identify the molecular basis of 
      this disease, 12 Italian families were studied by linkage analysis and mutation 
      screening. Flow cytometry evaluations of platelet membrane glycoproteins (GPs) 
      were also performed. Linkage analysis in 2 large families localized the gene to 
      chromosome 17p, in an interval containing an excellent candidate, the GPIbalpha 
      gene. GPIbalpha, together with other proteins, constitutes the plasma von 
      Willebrand factor (vWF) receptor, which is altered in Bernard-Soulier syndrome 
      (BSS). In 6 of 12 families, a heterozygous Ala156Val missense substitution was 
      identified. Platelet membrane GP studies were performed in 10 patients. Eight 
      were distinguished by a reduction of GPs comparable to that found in a BSS 
      heterozygous condition, whereas the other 2, without the Ala156Val mutation, had 
      a normal content of platelet GPs. In conclusion, the current study provides 
      evidence that most (10 of 12) patients with an original diagnosis of autosomal 
      dominant macrothrombocytopenia shared clinical and molecular features with the 
      heterozygous BSS phenotype. The remaining 2 affected subjects represented 
      patients with "true" autosomal dominant macrothrombocytopenia; the GPIb/IX/V 
      complex was normally distributed on the surface of their platelets. Thus, the 
      diagnosis of heterozygous BSS must always be suspected in patients with inherited 
      thrombocytopenia and platelet macrocytosis.
FAU - Savoia, A
AU  - Savoia A
AD  - Medical Genetics Service, IRCCS Hospital CSS, Foggia, Italy.
FAU - Balduini, C L
AU  - Balduini CL
FAU - Savino, M
AU  - Savino M
FAU - Noris, P
AU  - Noris P
FAU - Del Vecchio, M
AU  - Del Vecchio M
FAU - Perrotta, S
AU  - Perrotta S
FAU - Belletti, S
AU  - Belletti S
FAU - Poggi
AU  - Poggi
FAU - Iolascon, A
AU  - Iolascon A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Platelet Glycoprotein GPIb-IX Complex)
RN  - 0 (Platelet Membrane Glycoproteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Bernard-Soulier Syndrome/diagnosis/etiology/*genetics
MH  - Child
MH  - Child, Preschool
MH  - DNA Mutational Analysis
MH  - Diagnosis, Differential
MH  - Family Health
MH  - Female
MH  - Flow Cytometry
MH  - Genes, Dominant
MH  - Genetic Linkage
MH  - Heterozygote
MH  - Humans
MH  - Infant
MH  - Italy/epidemiology
MH  - Male
MH  - Middle Aged
MH  - Mutation, Missense
MH  - Pedigree
MH  - Platelet Glycoprotein GPIb-IX Complex/genetics
MH  - Platelet Membrane Glycoproteins/analysis
MH  - Thrombocytopenia/diagnosis/etiology/*genetics
EDAT- 2001/02/27 10:00
MHDA- 2001/04/21 10:01
CRDT- 2001/02/27 10:00
PHST- 2001/02/27 10:00 [pubmed]
PHST- 2001/04/21 10:01 [medline]
PHST- 2001/02/27 10:00 [entrez]
AID - S0006-4971(20)56253-8 [pii]
AID - 10.1182/blood.v97.5.1330 [doi]
PST - ppublish
SO  - Blood. 2001 Mar 1;97(5):1330-5. doi: 10.1182/blood.v97.5.1330.