TY - JOUR T1 - Gray platelet syndrome: Novel mutations of the NBEAL2 gene. JF - Am J Hematol Y1 - 2017 A1 - Bottega, Roberta A1 - Nicchia, Elena A1 - Alfano, Caterina A1 - Glembotsky, Ana C A1 - Pastore, Annalisa A1 - Bertaggia-Calderara, Debora A1 - Bisig, Bettina A1 - Duchosal, Michel A A1 - Arbesú, Guillermo A1 - Alberio, Lorenzo A1 - Heller, Paula G A1 - Savoia, Anna KW - Adult KW - Alleles KW - Blood Proteins KW - Child KW - Female KW - Gene Expression KW - Gene Frequency KW - Genotype KW - Gray Platelet Syndrome KW - Humans KW - Male KW - Mutation KW - Phenotype KW - Platelet Aggregation KW - Platelet Count KW - Platelet Membrane Glycoproteins VL - 92 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27870194?dopt=Abstract ER - TY - JOUR T1 - Mutations of RUNX1 in families with inherited thrombocytopenia. JF - Am J Hematol Y1 - 2017 A1 - De Rocco, Daniela A1 - Melazzini, Federica A1 - Marconi, Caterina A1 - Pecci, Alessandro A1 - Bottega, Roberta A1 - Gnan, Chiara A1 - Palombo, Flavia A1 - Giordano, Paola A1 - Coccioli, Maria Susanna A1 - Glembotsky, Ana C A1 - Heller, Paula G A1 - Seri, Marco A1 - Savoia, Anna A1 - Noris, Patrizia KW - Adult KW - Blood Platelets KW - Cell Size KW - Child KW - Child, Preschool KW - Core Binding Factor Alpha 2 Subunit KW - Female KW - Frameshift Mutation KW - Genes, Dominant KW - Heterozygote KW - Humans KW - Introns KW - Leukemia, Myeloid, Acute KW - Male KW - Middle Aged KW - Mutation, Missense KW - Protein Domains KW - RNA Splice Sites KW - Sequence Deletion KW - Thrombocythemia, Essential KW - Thrombopoietin KW - Transcriptional Activation KW - Young Adult VL - 92 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28240786?dopt=Abstract ER - TY - JOUR T1 - Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. JF - Haematologica Y1 - 2014 A1 - Noris, Patrizia A1 - Schlegel, Nicole A1 - Klersy, Catherine A1 - Heller, Paula G A1 - Civaschi, Elisa A1 - Pujol-Moix, Núria A1 - Fabris, Fabrizio A1 - Favier, Rémi A1 - Gresele, Paolo A1 - Latger-Cannard, Véronique A1 - Cuker, Adam A1 - Nurden, Paquita A1 - Greinacher, Andreas A1 - Cattaneo, Marco A1 - De Candia, Erica A1 - Pecci, Alessandro A1 - Hurtaud-Roux, Marie-Françoise A1 - Glembotsky, Ana C A1 - Muñiz-Diaz, Eduardo A1 - Randi, Maria Luigia A1 - Trillot, Nathalie A1 - Bury, Loredana A1 - Lecompte, Thomas A1 - Marconi, Caterina A1 - Savoia, Anna A1 - Balduini, Carlo L A1 - Bayart, Sophie A1 - Bauters, Anne A1 - Benabdallah-Guedira, Schéhérazade A1 - Boehlen, Françoise A1 - Borg, Jeanne-Yvonne A1 - Bottega, Roberta A1 - Bussel, James A1 - De Rocco, Daniela A1 - de Maistre, Emmanuel A1 - Faleschini, Michela A1 - Falcinelli, Emanuela A1 - Ferrari, Silvia A1 - Ferster, Alina A1 - Fierro, Tiziana A1 - Fleury, Dominique A1 - Fontana, Pierre A1 - James, Chloé A1 - Lanza, Francois A1 - Le Cam Duchez, Véronique A1 - Loffredo, Giuseppe A1 - Magini, Pamela A1 - Martin-Coignard, Dominique A1 - Menard, Fanny A1 - Mercier, Sandra A1 - Mezzasoma, Annamaria A1 - Minuz, Pietro A1 - Nichele, Ilaria A1 - Notarangelo, Lucia D A1 - Pippucci, Tommaso A1 - Podda, Gian Marco A1 - Pouymayou, Catherine A1 - Rigouzzo, Agnes A1 - Royer, Bruno A1 - Sie, Pierre A1 - Siguret, Virginie A1 - Trichet, Catherine A1 - Tucci, Alessandra A1 - Saposnik, Béatrice A1 - Veneri, Dino KW - Adult KW - Female KW - Humans KW - Infant, Newborn KW - Pregnancy KW - Pregnancy Complications, Hematologic KW - Retrospective Studies KW - Thrombocytopenia KW - Young Adult AB -

Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 × 10(9)/L.

VL - 99 IS - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24763399?dopt=Abstract ER - TY - JOUR T1 - MYH9-related disease: a novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations. JF - Hum Mutat Y1 - 2014 A1 - Pecci, Alessandro A1 - Klersy, Catherine A1 - Gresele, Paolo A1 - Lee, Kieran J D A1 - De Rocco, Daniela A1 - Bozzi, Valeria A1 - Russo, Giovanna A1 - Heller, Paula G A1 - Loffredo, Giuseppe A1 - Ballmaier, Matthias A1 - Fabris, Fabrizio A1 - Beggiato, Eloise A1 - Kahr, Walter H A A1 - Pujol-Moix, Núria A1 - Platokouki, Helen A1 - Van Geet, Christel A1 - Noris, Patrizia A1 - Yerram, Preethi A1 - Hermans, Cedric A1 - Gerber, Bernhard A1 - Economou, Marina A1 - De Groot, Marco A1 - Zieger, Barbara A1 - De Candia, Erica A1 - Fraticelli, Vincenzo A1 - Kersseboom, Rogier A1 - Piccoli, Giorgina B A1 - Zimmermann, Stefanie A1 - Fierro, Tiziana A1 - Glembotsky, Ana C A1 - Vianello, Fabrizio A1 - Zaninetti, Carlo A1 - Nicchia, Elena A1 - Güthner, Christiane A1 - Baronci, Carlo A1 - Seri, Marco A1 - Knight, Peter J A1 - Balduini, Carlo L A1 - Savoia, Anna KW - Adult KW - Age of Onset KW - Amino Acid Substitution KW - Cataract KW - Female KW - Genetic Association Studies KW - Genotype KW - Hearing Loss, Sensorineural KW - Humans KW - Italy KW - Linear Models KW - Male KW - Molecular Motor Proteins KW - Mutation KW - Myosin Heavy Chains KW - Phenotype KW - Risk Factors KW - Thrombocytopenia AB -

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' clinical management and genetic counseling and are discussed in view of molecular pathogenesis of MYH9-RD.

VL - 35 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24186861?dopt=Abstract ER - TY - JOUR T1 - MYH9-related disease: five novel mutations expanding the spectrum of causative mutations and confirming genotype/phenotype correlations. JF - Eur J Med Genet Y1 - 2013 A1 - De Rocco, Daniela A1 - Zieger, Barbara A1 - Platokouki, Helen A1 - Heller, Paula G A1 - Pastore, Annalisa A1 - Bottega, Roberta A1 - Noris, Patrizia A1 - Barozzi, Serena A1 - Glembotsky, Ana C A1 - Pergantou, Helen A1 - Balduini, Carlo L A1 - Savoia, Anna A1 - Pecci, Alessandro KW - Adolescent KW - Adult KW - Amino Acid Sequence KW - Amino Acid Substitution KW - Base Sequence KW - Child KW - Child, Preschool KW - Exons KW - Female KW - Genes, Dominant KW - Genetic Association Studies KW - Humans KW - Male KW - Middle Aged KW - Models, Molecular KW - Molecular Motor Proteins KW - Molecular Sequence Data KW - Mutation KW - Myosin Heavy Chains KW - Pedigree KW - Protein Conformation KW - Sequence Alignment KW - Syndrome KW - Thrombocytopenia KW - Young Adult AB -

MYH9-related disease (MYH9-RD) is a rare autosomal dominant syndromic disorder caused by mutations in MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (myosin-9). MYH9-RD is characterized by congenital macrothrombocytopenia and typical inclusion bodies in neutrophils associated with a variable risk of developing sensorineural deafness, presenile cataract, and/or progressive nephropathy. The spectrum of mutations responsible for MYH9-RD is limited. We report five families, each with a novel MYH9 mutation. Two mutations, p.Val34Gly and p.Arg702Ser, affect the motor domain of myosin-9, whereas the other three, p.Met847_Glu853dup, p.Lys1048_Glu1054del, and p.Asp1447Tyr, hit the coiled-coil tail domain of the protein. The motor domain mutations were associated with more severe clinical phenotypes than those in the tail domain.

VL - 56 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23123319?dopt=Abstract ER -