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

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).

%B Am J Hematol %V 94 %P 216-222 %8 2019 Feb %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/30456824?dopt=Abstract %R 10.1002/ajh.25353 %0 Journal Article %J Blood %D 2019 %T Loss-of-function mutations in cause a new form of inherited thrombocytopenia. %A Marconi, Caterina %A Di Buduo, Christian A %A LeVine, Kellie %A Barozzi, Serena %A Faleschini, Michela %A Bozzi, Valeria %A Palombo, Flavia %A McKinstry, Spencer %A Lassandro, Giuseppe %A Giordano, Paola %A Noris, Patrizia %A Balduini, Carlo L %A Savoia, Anna %A Balduini, Alessandra %A Pippucci, Tommaso %A Seri, Marco %A Katsanis, Nicholas %A Pecci, Alessandro %X

Inherited thrombocytopenias (ITs) are a heterogeneous group of disorders characterized by low platelet count that may result in bleeding tendency. Despite progress being made in defining the genetic causes of ITs, nearly 50% of patients with familial thrombocytopenia are affected with forms of unknown origin. Here, through exome sequencing of 2 siblings with autosomal-recessive thrombocytopenia, we identified biallelic loss-of-function variants in This gene encodes for a receptor-like PTP, PTPRJ (or CD148), which is expressed abundantly in platelets and megakaryocytes. Consistent with the predicted effects of the variants, both probands have an almost complete loss of PTPRJ at the messenger RNA and protein levels. To investigate the pathogenic role of PTPRJ deficiency in hematopoiesis in vivo, we carried out CRISPR/Cas9-mediated ablation of (the ortholog of human ) in zebrafish, which induced a significantly decreased number of CD41 thrombocytes in vivo. Moreover, megakaryocytes of our patients showed impaired maturation and profound defects in SDF1-driven migration and formation of proplatelets in vitro. Silencing of in a human megakaryocytic cell line reproduced the functional defects observed in patients' megakaryocytes. The disorder caused by mutations presented as a nonsyndromic thrombocytopenia characterized by spontaneous bleeding, small-sized platelets, and impaired platelet responses to the GPVI agonists collagen and convulxin. These platelet functional defects could be attributed to reduced activation of Src family kinases. Taken together, our data identify a new form of IT and highlight a hitherto unknown fundamental role for PTPRJ in platelet biogenesis.

%B Blood %V 133 %P 1346-1357 %8 2019 Mar 21 %G eng %N 12 %1 http://www.ncbi.nlm.nih.gov/pubmed/30591527?dopt=Abstract %R 10.1182/blood-2018-07-859496