TY - JOUR T1 - Idiopathic neutropenia of infancy: Data from the Italian Neutropenia Registry. JF - Am J Hematol Y1 - 2019 A1 - Farruggia, Piero A1 - Fioredda, Francesca A1 - Puccio, Giuseppe A1 - Onofrillo, Daniela A1 - Russo, Giovanna A1 - Barone, Angelica A1 - Bonanomi, Sonia A1 - Boscarol, Gianluca A1 - Finocchi, Andrea A1 - Ghilardi, Roberta A1 - Giordano, Paola A1 - Ladogana, Saverio A1 - Lassandro, Giuseppe A1 - Luti, Laura A1 - Lanza, Tiziana A1 - Mandaglio, Rosalba A1 - Marra, Nicoletta A1 - Martire, Baldassare A1 - Mastrodicasa, Elena A1 - Motta, Milena A1 - Notarangelo, Lucia Dora A1 - Pillon, Marta A1 - Porretti, Laura A1 - Serafinelli, Jessica A1 - Trizzino, Angela A1 - Tucci, Fabio A1 - Veltroni, Marinella A1 - Verzegnassi, Federico A1 - Ramenghi, Ugo A1 - Dufour, Carlo AB -

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).

VL - 94 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/30456824?dopt=Abstract ER - TY - JOUR T1 - Autoimmune neutropenia of childhood secondary to other autoimmune disorders: Data from the Italian neutropenia registry. JF - Am J Hematol Y1 - 2017 A1 - Farruggia, Piero A1 - Puccio, Giuseppe A1 - Fioredda, Francesca A1 - Lanza, Tiziana A1 - Porretti, Laura A1 - Ramenghi, Ugo A1 - Barone, Angelica A1 - Bonanomi, Sonia A1 - Finocchi, Andrea A1 - Ghilardi, Roberta A1 - Ladogana, Saverio A1 - Marra, Nicoletta A1 - Martire, Baldassare A1 - Notarangelo, Lucia Dora A1 - Onofrillo, Daniela A1 - Pillon, Marta A1 - Russo, Giovanna A1 - Lo Valvo, Laura A1 - Serafinelli, Jessica A1 - Tucci, Fabio A1 - Zunica, Fiammetta A1 - Verzegnassi, Federico A1 - Dufour, Carlo KW - Autoimmune Diseases KW - Child KW - Disease Susceptibility KW - Female KW - Humans KW - Immunoglobulins, Intravenous KW - Immunosuppressive Agents KW - Infant, Newborn KW - Infant, Premature KW - Infant, Premature, Diseases KW - Italy KW - Male KW - Neutropenia KW - Prevalence KW - Registries VL - 92 IS - 9 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28567966?dopt=Abstract ER - TY - JOUR T1 - Are all cases of paediatric essential thrombocythaemia really myeloproliferative neoplasms? Analysis of a large cohort. JF - Br J Haematol Y1 - 2015 A1 - Randi, Maria L A1 - Geranio, Giulia A1 - Bertozzi, Irene A1 - Micalizzi, Concetta A1 - Ramenghi, Ugo A1 - Tucci, Fabio A1 - Notarangelo, Lucia D A1 - Ladogana, Saverio A1 - Menna, Giuseppe A1 - Giordano, Paola A1 - Consarino, Caterina A1 - Farruggia, Piero A1 - Zanazzo, Giulio A A1 - Fiori, Giovanni M A1 - Burnelli, Roberta A1 - Russo, Giovanna A1 - Jankovich, Momcilo A1 - Peroni, Edoardo A1 - Duner, Elena A1 - Basso, Giuseppe A1 - Fabris, Fabrizio A1 - Putti, Maria C KW - Adolescent KW - Adult KW - Amino Acid Substitution KW - Child KW - Child, Preschool KW - Cohort Studies KW - Female KW - Hematologic Neoplasms KW - Humans KW - Infant KW - Janus Kinase 2 KW - Male KW - Mutation, Missense KW - Neoplasm Proteins KW - Thrombocythemia, Essential AB -

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 (25·8%) 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 (74·2%) 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.

VL - 169 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25716342?dopt=Abstract ER - TY - JOUR T1 - Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology. JF - Haematologica Y1 - 2014 A1 - De Rocco, Daniela A1 - Bottega, Roberta A1 - Cappelli, Enrico A1 - Cavani, Simona A1 - Criscuolo, Maria A1 - Nicchia, Elena A1 - Corsolini, Fabio A1 - Greco, Chiara A1 - Borriello, Adriana A1 - Svahn, Johanna A1 - Pillon, Marta A1 - Mecucci, Cristina A1 - Casazza, Gabriella A1 - Verzegnassi, Federico A1 - Cugno, Chiara A1 - Locasciulli, Anna A1 - Farruggia, Piero A1 - Longoni, Daniela A1 - Ramenghi, Ugo A1 - Barberi, Walter A1 - Tucci, Fabio A1 - Perrotta, Silverio A1 - Grammatico, Paola A1 - Hanenberg, Helmut A1 - Della Ragione, Fulvio A1 - Dufour, Carlo A1 - Savoia, Anna KW - Amino Acid Substitution KW - Cell Line KW - Cohort Studies KW - Computational Biology KW - Databases, Nucleic Acid KW - Fanconi Anemia KW - Fanconi Anemia Complementation Group Proteins KW - Founder Effect KW - Genotype KW - Humans KW - Italy KW - Mosaicism KW - Mutation KW - Polymorphism, Single Nucleotide AB -

Fanconi anemia is an inherited disease characterized by congenital malformations, pancytopenia, cancer predisposition, and sensitivity to cross-linking agents. The molecular diagnosis of Fanconi anemia is relatively complex for several aspects including genetic heterogeneity with mutations in at least 16 different genes. In this paper, we report the mutations identified in 100 unrelated probands enrolled into the National Network of the Italian Association of Pediatric Hematoly and Oncology. In approximately half of these cases, mutational screening was carried out after retroviral complementation analyses or protein analysis. In the other half, the analysis was performed on the most frequently mutated genes or using a next generation sequencing approach. We identified 108 distinct variants of the FANCA, FANCG, FANCC, FANCD2, and FANCB genes in 85, 9, 3, 2, and 1 families, respectively. Despite the relatively high number of private mutations, 45 of which are novel Fanconi anemia alleles, 26% of the FANCA alleles are due to 5 distinct mutations. Most of the mutations are large genomic deletions and nonsense or frameshift mutations, although we identified a series of missense mutations, whose pathogenetic role was not always certain. The molecular diagnosis of Fanconi anemia is still a tiered procedure that requires identifying candidate genes to avoid useless sequencing. Introduction of next generation sequencing strategies will greatly improve the diagnostic process, allowing a rapid analysis of all the genes.

VL - 99 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24584348?dopt=Abstract ER -