title: Clinical and laboratory features of 103 patients from 42 Italian families with inherited thrombocytopenia derived from the monoallelic Ala156Val mutation of GPIbα (Bolzano mutation).
abstract: BACKGROUND
  Bernard-Soulier syndrome is a very rare form of inherited thrombocytopenia that derives from mutations in GPIbα, GPIbβ, or GPIX and is typically inherited as a recessive disease. However, some years ago it was shown that the monoallelic c.515C>T transition in the GPIBA gene (Bolzano mutation) was responsible for macrothrombocytopenia in a few Italian patients.
  
  
  METHODS
  Over the past 10 years, we have searched for the Bolzano mutation in all subjects referred to our institutions because of an autosomal, dominant form of thrombocytopenia of unknown origin.
  
  
  RESULTS
  We identified 42 new Italian families (103 cases) with a thrombocytopenia induced by monoallelic Bolzano mutation. Analyses of the geographic origin of affected pedigrees and haplotypes indicated that this mutation originated in southern Italy. Although the clinical expression was variable, patients with this mutation typically had a mild form of Bernard-Soulier syndrome with mild thrombocytopenia and bleeding tendency. The most indicative laboratory findings were enlarged platelets and reduced GPIb/IX/V platelet expression; in vitro platelet aggregation was normal in nearly all of the cases.
  
  
  CONCLUSIONS
  Our study indicates that monoallelic Bolzano mutation is the most frequent cause of inherited thrombocytopenia in Italy, affecting 20% of patients recruited at our institutions during the last 10 years. Because many people from southern Italy have emigrated during the last century, this mutation may have spread to other countries.
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy. c.balduini@smatteo.pv.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Noris
authors.forename: Silverio
authors.initials: S
authors.lastname: Perrotta
authors.forename: Roberta
authors.initials: R
authors.lastname: Bottega
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
authors.forename: Federica
authors.initials: F
authors.lastname: Melazzini
authors.forename: Elisa
authors.initials: E
authors.lastname: Civaschi
authors.forename: Sabina
authors.initials: S
authors.lastname: Russo
authors.forename: Silvana
authors.initials: S
authors.lastname: Magrin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Loffredo
authors.forename: Veronica
authors.initials: V
authors.lastname: Di Salvo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Russo
authors.forename: Maddalena
authors.initials: M
authors.lastname: Casale
authors.forename: Daniela
authors.initials: D
authors.lastname: De Rocco
authors.forename: Claudio
authors.initials: C
authors.lastname: Grignani
authors.forename: Marco
authors.initials: M
authors.lastname: Cattaneo
authors.forename: Carlo
authors.initials: C
authors.lastname: Baronci
authors.forename: Alfredo
authors.initials: A
authors.lastname: Dragani
authors.forename: Veronica
authors.initials: V
authors.lastname: Albano
authors.forename: Momcilo
authors.initials: M
authors.lastname: Jankovic
authors.forename: Saverio
authors.initials: S
authors.lastname: Scianguetta
authors.forename: Anna
authors.initials: A
authors.lastname: Savoia
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Balduini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001606:Bernard-Soulier Syndrome / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010974:Platelet Aggregation; D010976:Platelet Count; D019038:Platelet Glycoprotein GPIb-IX Complex; D011110:Polymorphism, Genetic; D013921:Thrombocytopenia / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D013926:Thrombopoietin / Q000097:blood; D014404:Tubulin / Q000235:genetics; D055815:Young Adult
chemical_list: D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D014404:Tubulin; C094990:adhesion receptor; D013926:Thrombopoietin