@article {10797, title = {Idiopathic neutropenia of infancy: Data from the Italian Neutropenia Registry.}, journal = {Am J Hematol}, volume = {94}, year = {2019}, month = {2019 Feb}, pages = {216-222}, abstract = {

Autoimmune neutropenia of infancy (AIN) is characterized by low risk of severe infection, tendency to spontaneously resolve and typically onset at <=4-5 years of age; it is due to auto-antibodies whose detection is often difficult. In case of negativity of 4 antineutrophils autoantibody tests, after having excluded ethnic, postinfection, drug induced, or congenital neutropenia, according to the Italian guidelines the patients will be defined as affected by "idiopathic neutropenia" (IN). We describe the characteristics of 85 IN patients enrolled in the Italian neutropenia registry: they were compared with 336 children affected by AIN. The 2 groups were clinically very similar and the main differences were detection age (later in IN), length of disease (longer in IN) and, among recovered patients, age of spontaneous recovery: the median age at resolution was 2.13 years in AINs and 3.03 years in INs (P = .00002). At bivariate analysis among AIN patients earlier detection age (P = .00013), male sex (P = .000748), absence of leucopenia (P = .0045), and absence of monocytosis (P = .0419) were significantly associated with earlier recovery; in the IN group only detection age (P = .013) and absence of monocytosis (P = .0333) were significant. At multivariate analysis detection age and absence of monocytosis were independently significant (P = 6.7e-05 and 4.4e-03, respectively) in the AIN group, whereas in the IN group only detection age stayed significant (P = .013).

}, issn = {1096-8652}, doi = {10.1002/ajh.25353}, author = {Farruggia, Piero and Fioredda, Francesca and Puccio, Giuseppe and Onofrillo, Daniela and Russo, Giovanna and Barone, Angelica and Bonanomi, Sonia and Boscarol, Gianluca and Finocchi, Andrea and Ghilardi, Roberta and Giordano, Paola and Ladogana, Saverio and Lassandro, Giuseppe and Luti, Laura and Lanza, Tiziana and Mandaglio, Rosalba and Marra, Nicoletta and Martire, Baldassare and Mastrodicasa, Elena and Motta, Milena and Notarangelo, Lucia Dora and Pillon, Marta and Porretti, Laura and Serafinelli, Jessica and Trizzino, Angela and Tucci, Fabio and Veltroni, Marinella and Verzegnassi, Federico and Ramenghi, Ugo and Dufour, Carlo} } @article {10421, title = {Hypomorphic FANCA mutations correlate with mild mitochondrial and clinical phenotype in Fanconi anemia.}, journal = {Haematologica}, volume = {103}, year = {2018}, month = {2018 Mar}, pages = {417-426}, abstract = {

Fanconi anemia is a rare disease characterized by congenital malformations, aplastic anemia, and predisposition to cancer. Despite the consolidated role of the Fanconi anemia proteins in DNA repair, their involvement in mitochondrial function is emerging. The purpose of this work was to assess whether the mitochondrial phenotype, independent of genomic integrity, could correlate with patient phenotype. We evaluated mitochondrial and clinical features of 11 affected individuals homozygous or compound heterozygous for p.His913Pro and p.Arg951Gln/Trp, the two residues of FANCA that are more frequently affected in our cohort of patients. Although p.His913Pro and p.Arg951Gln proteins are stably expressed in cytoplasm, they are unable to migrate in the nucleus, preventing cells from repairing DNA. In these cells, the electron transfer between respiring complex I-III is reduced and the ATP/AMP ratio is impaired with defective ATP production and AMP accumulation. These activities are intermediate between those observed in wild-type and FANCA-/- cells, suggesting that the variants at residues His913 and Arg951 are hypomorphic mutations. Consistent with these findings, the clinical phenotype of most of the patients carrying these mutations is mild. These data further support the recent finding that the Fanconi anemia proteins play a role in mitochondria, and open up possibilities for genotype/phenotype studies based on novel mitochondrial criteria.

}, issn = {1592-8721}, doi = {10.3324/haematol.2017.176131}, author = {Bottega, Roberta and Nicchia, Elena and Cappelli, Enrico and Ravera, Silvia and De Rocco, Daniela and Faleschini, Michela and Corsolini, Fabio and Pierri, Filomena and Calvillo, Michaela and Russo, Giovanna and Casazza, Gabriella and Ramenghi, Ugo and Farruggia, Piero and Dufour, Carlo and Savoia, Anna} } @article {10525, title = {Autoimmune neutropenia of childhood secondary to other autoimmune disorders: Data from the Italian neutropenia registry.}, journal = {Am J Hematol}, volume = {92}, year = {2017}, month = {2017 Sep}, pages = {E546-E549}, keywords = {Autoimmune Diseases, Child, Disease Susceptibility, Female, Humans, Immunoglobulins, Intravenous, Immunosuppressive Agents, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases, Italy, Male, Neutropenia, Prevalence, Registries}, issn = {1096-8652}, doi = {10.1002/ajh.24803}, author = {Farruggia, Piero and Puccio, Giuseppe and Fioredda, Francesca and Lanza, Tiziana and Porretti, Laura and Ramenghi, Ugo and Barone, Angelica and Bonanomi, Sonia and Finocchi, Andrea and Ghilardi, Roberta and Ladogana, Saverio and Marra, Nicoletta and Martire, Baldassare and Notarangelo, Lucia Dora and Onofrillo, Daniela and Pillon, Marta and Russo, Giovanna and Lo Valvo, Laura and Serafinelli, Jessica and Tucci, Fabio and Zunica, Fiammetta and Verzegnassi, Federico and Dufour, Carlo} } @article {10539, title = {Diagnosis and management of newly diagnosed childhood autoimmune haemolytic anaemia. Recommendations from the Red Cell Study Group of the Paediatric Haemato-Oncology Italian Association.}, journal = {Blood Transfus}, volume = {15}, year = {2017}, month = {2017 May}, pages = {259-267}, abstract = {

Autoimmune haemolytic anaemia is an uncommon disorder to which paediatric haematology centres take a variety of diagnostic and therapeutic approaches. The Red Cell Working Group of the Italian Association of Paediatric Onco-haematology (Associazione Italiana di Ematologia ed Oncologia Pediatrica, AIEOP) developed this document in order to collate expert opinions on the management of newly diagnosed childhood autoimmune haemolytic anaemia.The diagnostic process includes the direct and indirect antiglobulin tests; recommendations are given regarding further diagnostic tests, specifically in the cases that the direct and indirect antiglobulin tests are negative. Clear-cut definitions of clinical response are stated. Specific recommendations for treatment include: dosage of steroid therapy and tapering modality for warm autoimmune haemolytic anaemia; the choice of rituximab as first-line therapy for the rare primary transfusion-dependent cold autoimmune haemolytic anaemia; the indications for supportive therapy; the need for switching to second-line therapy. Each statement is provided with a score expressing the level of appropriateness and the agreement among participants.

}, keywords = {Anemia, Hemolytic, Autoimmune, Blood Transfusion, Child, Coombs Test, Disease Management, Hematology, Humans, Immunoglobulin M, Italy, Pediatrics, Societies, Medical, Steroids}, issn = {1723-2007}, doi = {10.2450/2016.0072-16}, author = {Ladogana, Saverio and Maruzzi, Matteo and Samperi, Piera and Perrotta, Silverio and Del Vecchio, Giovanni C and Notarangelo, Lucia D and Farruggia, Piero and Verzegnassi, Federico and Masera, Nicoletta and Saracco, Paola and Fasoli, Silvia and Miano, Maurizio and Girelli, Gabriella and Barcellini, Wilma and Zanella, Alberto and Russo, Giovanna} } @article {10526, title = {Retrospective study on the incidence and outcome of proven and probable invasive fungal infections in high-risk pediatric onco-hematological patients.}, journal = {Eur J Haematol}, volume = {99}, year = {2017}, month = {2017 Sep}, pages = {240-248}, abstract = {

BACKGROUND: Invasive fungal infection (IFI) is a cause of morbidity, mortality and increased health costs in children undergoing chemotherapy or hematopoietic stem cell transplant (HSCT).

METHODS: Multicenter, retrospective study to assess the incidence, outcome of proven and probable IFI (PP-IFI) in children treated for acute leukemia, non-Hodgkin lymphoma or who underwent HSCT from 2006 to 2012.

RESULTS: Over the 7-year period, 127 PP-IFI were diagnosed in 123 patients, median age of 9.7~years. The 1-year cumulative incidence was 2.5\% (CI 1.8-3.7) after frontline chemotherapy, 9.4\% (CI 5.8-15.0) after relapse, and 5.3\% (CI 3.9-7.1) after HSCT. Severe neutropenia was present in 98 (77\%) patients. Culture-proven agents were Candida spp., mostly non-albicans, 28, mold 23, whereas three proven IFI were identified by histopathology. Favorable response to treatment within 3~months from diagnosis was observed in 77 (89\%). The overall ninety-day probability of survival was 68\% (CI 59-76).

CONCLUSIONS: About two-thirds of pediatric patients with PP-IFI survived, regardless of whether the infection occurred after frontline chemotherapy, reinduction chemotherapy for disease relapse, or after HSCT. Further prospective studies are needed to define the impact of antifungal prophylaxis and early combination therapy on short-term overall survival.

}, keywords = {Adolescent, Antifungal Agents, Antineoplastic Combined Chemotherapy Protocols, Child, Child, Preschool, Drug Therapy, Combination, Female, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Incidence, Male, Mycoses, Patient Outcome Assessment, Retrospective Studies, Survival Analysis, Treatment Outcome}, issn = {1600-0609}, doi = {10.1111/ejh.12910}, author = {Cesaro, Simone and Tridello, Gloria and Castagnola, Elio and Calore, Elisabetta and Carraro, Francesca and Mariotti, Ilaria and Colombini, Antonella and Perruccio, Katia and Decembrino, Nunzia and Russo, Giovanna and Maximova, Natalia and Baretta, Valentina and Caselli, D{\'e}sir{\'e}e} } @article {7760, title = {Are all cases of paediatric essential thrombocythaemia really myeloproliferative neoplasms? Analysis of a large cohort.}, journal = {Br J Haematol}, volume = {169}, year = {2015}, month = {2015 May}, pages = {584-9}, abstract = {

Sporadic essential thrombocythaemia (ET) is rare in paediatrics, and the diagnostic and clinical approach to paediatric cases cannot be simply copied from experience with adults. Here, we assessed 89 children with a clinical diagnosis of ET and found that 23 patients (25{\textperiodcentered}8\%) had a clonal disease. The JAK2 V617F mutation was identified in 14 children, 1 child had the MPL W515L mutation, and 6 had CALR mutations. The monoclonal X-chromosome inactivation pattern was seen in six patients (two with JAK2 V617F and two with CALR mutations). The other 66 patients (74{\textperiodcentered}2\%) had persistent thrombocytosis with no clonality. There were no clinical or haematological differences between the clonal and non-clonal patients. The relative proportion of ET-specific mutations in the clonal children was much the same as in adults. The higher prevalence of non-clonal cases suggests that some patients may not have myeloproliferative neoplasms, with significant implications for their treatment.

}, keywords = {Adolescent, Adult, Amino Acid Substitution, Child, Child, Preschool, Cohort Studies, Female, Hematologic Neoplasms, Humans, Infant, Janus Kinase 2, Male, Mutation, Missense, Neoplasm Proteins, Thrombocythemia, Essential}, issn = {1365-2141}, doi = {10.1111/bjh.13329}, author = {Randi, Maria L and Geranio, Giulia and Bertozzi, Irene and Micalizzi, Concetta and Ramenghi, Ugo and Tucci, Fabio and Notarangelo, Lucia D and Ladogana, Saverio and Menna, Giuseppe and Giordano, Paola and Consarino, Caterina and Farruggia, Piero and Zanazzo, Giulio A and Fiori, Giovanni M and Burnelli, Roberta and Russo, Giovanna and Jankovich, Momcilo and Peroni, Edoardo and Duner, Elena and Basso, Giuseppe and Fabris, Fabrizio and Putti, Maria C} } @article {3550, title = {Mutations of cytochrome c identified in patients with thrombocytopenia THC4 affect both apoptosis and cellular bioenergetics.}, journal = {Biochim Biophys Acta}, volume = {1842}, year = {2014}, month = {2014 Feb}, pages = {269-74}, abstract = {

Inherited thrombocytopenias are heterogeneous diseases caused by at least 20 genes playing different role in the processes of megakaryopoiesis and platelet production. Some forms, such as thrombocytopenia 4 (THC4), are very rare and not well characterized. THC4 is an autosomal dominant mild thrombocytopenia described in only one large family from New Zealand and due to a mutation (G41S) of the somatic isoform of the cytochrome c (CYCS) gene. We report a novel CYCS mutation (Y48H) in patients from an Italian family. Similar to individuals carrying G41S, they have platelets of normal size and morphology, which are only partially reduced in number, but no prolonged bleeding episodes. In order to determine the pathogenetic consequences of Y48H, we studied the effects of the two CYCS mutations in yeast and mouse cellular models. In both cases, we found reduction of respiratory level and increased apoptotic rate, supporting the pathogenetic role of CYCS in thrombocytopenia.

}, keywords = {Amino Acid Sequence, Animals, Apoptosis, Base Sequence, Cells, Cultured, Child, Preschool, Cytochromes c, DNA Mutational Analysis, Embryo, Mammalian, Energy Metabolism, Family Health, Female, Fibroblasts, Humans, Lung, Male, Mice, Molecular Sequence Data, Mutation, Missense, Oxygen Consumption, Pedigree, Saccharomyces cerevisiae, Sequence Homology, Amino Acid, Thrombocytopenia}, issn = {0006-3002}, doi = {10.1016/j.bbadis.2013.12.002}, author = {De Rocco, Daniela and Cerqua, Cristina and Goffrini, Paola and Russo, Giovanna and Pastore, Annalisa and Meloni, Francesca and Nicchia, Elena and Moraes, Carlos T and Pecci, Alessandro and Salviati, Leonardo and Savoia, Anna} } @article {3635, title = {MYH9-related disease: a novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations.}, journal = {Hum Mutat}, volume = {35}, year = {2014}, month = {2014 Feb}, pages = {236-47}, abstract = {

MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in the gene for nonmuscle myosin heavy chain IIA (NMMHC-IIA). MYH9-RD is characterized by a considerable variability in clinical evolution: patients present at birth with only thrombocytopenia, but some of them subsequently develop sensorineural deafness, cataract, and/or nephropathy often leading to end-stage renal disease (ESRD). We searched for genotype-phenotype correlations in the largest series of consecutive MYH9-RD patients collected so far (255 cases from 121 families). Association of genotypes with noncongenital features was assessed by a generalized linear regression model. The analysis defined disease evolution associated to seven different MYH9 genotypes that are responsible for 85\% of MYH9-RD cases. Mutations hitting residue R702 demonstrated a complete penetrance for early-onset ESRD and deafness. The p.D1424H substitution associated with high risk of developing all the noncongenital manifestations of disease. Mutations hitting a distinct hydrophobic seam in the NMMHC-IIA head domain or substitutions at R1165 associated with high risk of deafness but low risk of nephropathy or cataract. Patients with p.E1841K, p.D1424N, and C-terminal deletions had low risk of noncongenital defects. These findings are essential to patients{\textquoteright} clinical management and genetic counseling and are discussed in view of molecular pathogenesis of MYH9-RD.

}, keywords = {Adult, Age of Onset, Amino Acid Substitution, Cataract, Female, Genetic Association Studies, Genotype, Hearing Loss, Sensorineural, Humans, Italy, Linear Models, Male, Molecular Motor Proteins, Mutation, Myosin Heavy Chains, Phenotype, Risk Factors, Thrombocytopenia}, issn = {1098-1004}, doi = {10.1002/humu.22476}, author = {Pecci, Alessandro and Klersy, Catherine and Gresele, Paolo and Lee, Kieran J D and De Rocco, Daniela and Bozzi, Valeria and Russo, Giovanna and Heller, Paula G and Loffredo, Giuseppe and Ballmaier, Matthias and Fabris, Fabrizio and Beggiato, Eloise and Kahr, Walter H A and Pujol-Moix, N{\'u}ria and Platokouki, Helen and Van Geet, Christel and Noris, Patrizia and Yerram, Preethi and Hermans, Cedric and Gerber, Bernhard and Economou, Marina and De Groot, Marco and Zieger, Barbara and De Candia, Erica and Fraticelli, Vincenzo and Kersseboom, Rogier and Piccoli, Giorgina B and Zimmermann, Stefanie and Fierro, Tiziana and Glembotsky, Ana C and Vianello, Fabrizio and Zaninetti, Carlo and Nicchia, Elena and G{\"u}thner, Christiane and Baronci, Carlo and Seri, Marco and Knight, Peter J and Balduini, Carlo L and Savoia, Anna} } @article {3634, title = {Platelet diameters in inherited thrombocytopenias: analysis of 376 patients with all known disorders.}, journal = {Blood}, volume = {124}, year = {2014}, month = {2014 Aug 7}, pages = {e4-e10}, abstract = {

Abnormalities of platelet size are one of the distinguishing features of inherited thrombocytopenias (ITs), and evaluation of blood films is recommended as an essential step for differential diagnosis of these disorders. Nevertheless, what we presently know about this subject is derived mainly from anecdotal evidence. To improve knowledge in this field, we evaluated platelet size on blood films obtained from 376 patients with all 19 forms of IT identified so far and found that these conditions differ not only in mean platelet diameter, but also in platelet diameter distribution width and the percentage of platelets with increased or reduced diameters. On the basis of these findings, we propose a new classification of ITs according to platelet size. It distinguishes forms with giant platelets, with large platelets, with normal or slightly increased platelet size, and with normal or slightly decreased platelet size. We also measured platelet diameters in 87 patients with immune thrombocytopenia and identified cutoff values for mean platelet diameter and the percentage of platelets with increased or reduced size that have good diagnostic accuracy in differentiating ITs with giant platelets and with normal or slightly decreased platelet size from immune thrombocytopenia and all other forms of IT.

}, keywords = {Adolescent, Adult, Blood Platelets, Case-Control Studies, Cell Size, Child, Child, Preschool, Diagnosis, Differential, Female, Hearing Loss, Sensorineural, Humans, Infant, Male, Middle Aged, Molecular Motor Proteins, Mutation, Myosin Heavy Chains, Purpura, Thrombocytopenic, Idiopathic, Thrombocytopenia, Young Adult}, issn = {1528-0020}, doi = {10.1182/blood-2014-03-564328}, author = {Noris, Patrizia and Biino, Ginevra and Pecci, Alessandro and Civaschi, Elisa and Savoia, Anna and Seri, Marco and Melazzini, Federica and Loffredo, Giuseppe and Russo, Giovanna and Bozzi, Valeria and Notarangelo, Lucia Dora and Gresele, Paolo and Heller, Paula G and Pujol-Moix, N{\'u}ria and Kunishima, Shinji and Cattaneo, Marco and Bussel, James and De Candia, Erica and Cagioni, Claudia and Ramenghi, Ugo and Barozzi, Serena and Fabris, Fabrizio and Balduini, Carlo L} } @article {3608, title = {Single-day trimethoprim/sulfamethoxazole prophylaxis for Pneumocystis pneumonia in children with cancer.}, journal = {J Pediatr}, volume = {164}, year = {2014}, month = {2014 Feb}, pages = {389-92.e1}, abstract = {

OBJECTIVE: To determine whether a simplified, 1-day/week regimen of trimethoprim/sulfamethoxazole is sufficient to prevent Pneumocystis (jirovecii [carinii]) pneumonia (PCP). Current recommended regimens for prophylaxis against PCP range from daily administration to 3 consecutive days per week dosing.

STUDY DESIGN: A prospective survey of the regimens adopted for the PCP prophylaxis in all patients treated for childhood cancer at pediatric hematology-oncology centers of the Associazione Italiana Ematologia Oncologia Pediatrica.

RESULTS: The 20 centers participating in the study reported a total of 2466 patients, including 1093 with solid tumor and 1373 with leukemia/lymphoma (or primary immunodeficiency; n = 2). Of these patients, 1371 (55.6\%) received the 3-day/week prophylaxis regimen, 406 (16.5\%) received the 2-day/week regimen, and 689 (27.9\%), including 439 with leukemia/lymphoma, received the 1-day/week regimen. Overall, only 2 cases of PCP (0.08\%) were reported, both in the 2-day/week group. By intention to treat, the cumulative incidence of PCP at 3 years was 0.09\% overall (95\% CI, 0.00-0.40\%) and 0.51\% for the 2-day/week group (95\% CI, 0.10\%-2.00\%). Remarkably, both patients who failed had withdrawn from prophylaxis.

CONCLUSION: A single-day course of prophylaxis with trimethoprim/sulfamethoxazole may be sufficient to prevent PCP in children with cancer undergoing intensive chemotherapy regimens. This simplified strategy might have implications for the emerging need for PCP prophylaxis in other patients subjected to the increased use of biological and nonbiological agents that induce higher levels of immune suppression, such as those with rheumatic diseases.

}, keywords = {Anti-Infective Agents, Child, Dose-Response Relationship, Drug, Drug Administration Schedule, Follow-Up Studies, Hematologic Neoplasms, Humans, Incidence, Italy, Pneumocystis carinii, Pneumonia, Pneumocystis, Prospective Studies, Treatment Outcome, Trimethoprim, Sulfamethoxazole Drug Combination}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2013.10.021}, author = {Caselli, D{\'e}sir{\'e}e and Petris, Maria Grazia and Rondelli, Roberto and Carraro, Francesca and Colombini, Antonella and Muggeo, Paola and Ziino, Ottavio and Melchionda, Fraia and Russo, Giovanna and Pierani, Paolo and Soncini, Elena and DeSantis, Raffaella and Zanazzo, Giulio and Barone, Angelica and Cesaro, Simone and Cellini, Monica and Mura, Rossella and Milano, Giuseppe M and Meazza, Cristina and Cicalese, Maria P and Tropia, Serena and De Masi, Salvatore and Castagnola, Elio and Aric{\`o}, Maurizio} } @article {3495, title = {Organizing national responses for rare blood disorders: the Italian experience with sickle cell disease in childhood.}, journal = {Orphanet J Rare Dis}, volume = {8}, year = {2013}, month = {2013}, pages = {169}, abstract = {

BACKGROUND: Sickle cell disease (SCD) is the most frequent hemoglobinopathy worldwide but remains a rare blood disorder in most western countries. Recommendations for standard of care have been produced in the United States, the United Kingdom and France, where this disease is relatively frequent because of earlier immigration from Africa. These recommendations have changed the clinical course of SCD but can be difficult to apply in other contexts. The Italian Association of Pediatric Hematology Oncology (AIEOP) decided to develop a common national response to the rising number of SCD patients in Italy with the following objectives: 1) to create a national working group focused on pediatric SCD, and 2) to develop tailored guidelines for the management of SCD that could be accessed and practiced by those involved in the care of children with SCD in Italy.

METHODS: Guidelines, adapted to the Italian social context and health system, were developed by 22 pediatric hematologists representing 54 AIEOP centers across Italy. The group met five times for a total of 128~hours in 22~months; documents and opinions were circulated via web.

RESULTS: Recommendations regarding the prevention and treatment of the most relevant complications of SCD in childhood adapted to the Italian context and health system were produced.

CONCLUSIONS: Creating a network of physicians involved in the day-to-day care of children with SCD is feasible in a country where it remains rare. Providing hematologists, primary and secondary care physicians, and caregivers across the country with web-based guidelines for the management of SCD tailored to the Italian context is the first step in building a sustainable response to a rare but emerging childhood blood disorder and in implementing the World Health Organization{\textquoteright}s suggestion "to design (and) implement {\textellipsis} comprehensive national integrated programs for the prevention and management of SCD".

}, keywords = {Adolescent, Anemia, Sickle Cell, Child, Child, Preschool, Disease Management, Female, Hematologic Diseases, Humans, Infant, Infant, Newborn, Italy, Male, Neonatal Screening, Rare Diseases}, issn = {1750-1172}, doi = {10.1186/1750-1172-8-169}, author = {Colombatti, Raffaella and Perrotta, Silverio and Samperi, Piera and Casale, Maddalena and Masera, Nicoletta and Palazzi, Giovanni and Sainati, Laura and Russo, Giovanna} } @article {1922, 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).}, journal = {Haematologica}, volume = {97}, year = {2012}, month = {2012 Jan}, pages = {82-8}, 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.

DESIGN AND 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.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Bernard-Soulier Syndrome, Child, Child, Preschool, Family Health, Female, Heterozygote, Humans, Infant, Italy, Male, Membrane Glycoproteins, Middle Aged, Mutation, Missense, Platelet Aggregation, Platelet Count, Platelet Glycoprotein GPIb-IX Complex, Polymorphism, Genetic, Thrombocytopenia, Thrombopoietin, Tubulin, Young Adult}, issn = {1592-8721}, doi = {10.3324/haematol.2011.050682}, author = {Noris, Patrizia and Perrotta, Silverio and Bottega, Roberta and Pecci, Alessandro and Melazzini, Federica and Civaschi, Elisa and Russo, Sabina and Magrin, Silvana and Loffredo, Giuseppe and Di Salvo, Veronica and Russo, Giovanna and Casale, Maddalena and De Rocco, Daniela and Grignani, Claudio and Cattaneo, Marco and Baronci, Carlo and Dragani, Alfredo and Albano, Veronica and Jankovic, Momcilo and Scianguetta, Saverio and Savoia, Anna and Balduini, Carlo L} }