@article {10546, title = {Mutations of RUNX1 in families with inherited thrombocytopenia.}, journal = {Am J Hematol}, volume = {92}, year = {2017}, month = {2017 06}, pages = {E86-E88}, keywords = {Adult, Blood Platelets, Cell Size, Child, Child, Preschool, Core Binding Factor Alpha 2 Subunit, Female, Frameshift Mutation, Genes, Dominant, Heterozygote, Humans, Introns, Leukemia, Myeloid, Acute, Male, Middle Aged, Mutation, Missense, Protein Domains, RNA Splice Sites, Sequence Deletion, Thrombocythemia, Essential, Thrombopoietin, Transcriptional Activation, Young Adult}, issn = {1096-8652}, doi = {10.1002/ajh.24703}, author = {De Rocco, Daniela and Melazzini, Federica and Marconi, Caterina and Pecci, Alessandro and Bottega, Roberta and Gnan, Chiara and Palombo, Flavia and Giordano, Paola and Coccioli, Maria Susanna and Glembotsky, Ana C and Heller, Paula G and Seri, Marco and Savoia, Anna and Noris, Patrizia} } @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 {1736, title = {Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: analysis of 78 patients from 21 families.}, journal = {Blood}, volume = {117}, year = {2011}, month = {2011 Jun 16}, pages = {6673-80}, abstract = {

Until recently, thrombocytopenia 2 (THC2) was considered an exceedingly rare form of autosomal dominant thrombocytopenia and only 2 families were known. However, we recently identified mutations in the 5{\textquoteright}-untranslated region of the ANKRD26 gene in 9 THC2 families. Here we report on 12 additional pedigrees with ANKRD26 mutations, 6 of which are new. Because THC2 affected 21 of the 210 families in our database, it has to be considered one of the less rare forms of inherited thrombocytopenia. Analysis of all 21 families with ANKRD26 mutations identified to date revealed that thrombocytopenia and bleeding tendency were usually mild. Nearly all patients had no platelet macrocytosis, and this characteristic distinguishes THC2 from most other forms of inherited thrombocytopenia. In the majority of cases, platelets were deficient in glycoprotein Ia and α-granules, whereas in vitro platelet aggregation was normal. Bone marrow examination and serum thrombopoietin levels suggested that thrombocytopenia was derived from dysmegakaryopoiesis. Unexplained high values of hemoglobin and leukocytes were observed in a few cases. An unexpected finding that warrants further investigation was a high incidence of acute leukemia. Given the scarcity of distinctive characteristics, the ANKRD26-related thrombocytopenia has to be taken into consideration in the differential diagnosis of isolated thrombocytopenias.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Ankyrin Repeat, Child, Cohort Studies, Family, Female, Gene Frequency, Humans, Inheritance Patterns, Male, Middle Aged, Mutation, Pedigree, Thrombocytopenia, Transcription Factors, Young Adult}, issn = {1528-0020}, doi = {10.1182/blood-2011-02-336537}, author = {Noris, Patrizia and Perrotta, Silverio and Seri, Marco and Pecci, Alessandro and Gnan, Chiara and Loffredo, Giuseppe and Pujol-Moix, N{\'u}ria and Zecca, Marco and Scognamiglio, Francesca and De Rocco, Daniela and Punzo, Francesca and Melazzini, Federica and Scianguetta, Saverio and Casale, Maddalena and Marconi, Caterina and Pippucci, Tommaso and Amendola, Giovanni and Notarangelo, Lucia D and Klersy, Catherine and Civaschi, Elisa and Balduini, Carlo L and Savoia, Anna} } @article {1688, title = {Mutations in the 5{\textquoteright} UTR of ANKRD26, the ankirin repeat domain 26 gene, cause an autosomal-dominant form of inherited thrombocytopenia, THC2.}, journal = {Am J Hum Genet}, volume = {88}, year = {2011}, month = {2011 Jan 7}, pages = {115-20}, abstract = {

THC2, an autosomal-dominant thrombocytopenia described so far in only two families, has been ascribed to mutations in MASTL or ACBD5. Here, we show that ANKRD26, another gene within the THC2 locus, and neither MASTL nor ACBD5, is mutated in eight unrelated families. ANKRD26 was also found to be mutated in the family previously reported to have an ACBD5 mutation. We identified six different ANKRD26 mutations, which were clustered in a highly conserved 19~bp sequence located in the 5{\textquoteright} untranslated region. Mutations were not detected in 500 controls and are absent from the 1000 Genomes database. Available data from an animal model and Dr.~Watson{\textquoteright}s genome give evidence against haploinsufficiency as the pathogenetic mechanism for ANKRD26-mediated thrombocytopenia. The luciferase reporter assay suggests that these 5{\textquoteright} UTR mutations might enhance ANKRD26 expression. ANKRD26 is the ancestor of a family of primate-specific genes termed POTE, which have been recently identified as a family of proapoptotic proteins. Dysregulation of apoptosis might therefore be the pathogenetic mechanism, as demonstrated for another thrombocytopenia, THC4. Further investigation is needed to provide evidence supporting this hypothesis.

}, keywords = {Ankyrin Repeat, Base Sequence, Chromosome Breakage, Chromosome Disorders, Conserved Sequence, Female, Genes, Dominant, Genetic Loci, Haploinsufficiency, Humans, Male, Molecular Sequence Data, Mutation, Pedigree, Thrombocytopenia}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2010.12.006}, author = {Pippucci, Tommaso and Savoia, Anna and Perrotta, Silverio and Pujol-Moix, N{\'u}ria and Noris, Patrizia and Castegnaro, Giovanni and Pecci, Alessandro and Gnan, Chiara and Punzo, Francesca and Marconi, Caterina and Gherardi, Samuele and Loffredo, Giuseppe and De Rocco, Daniela and Scianguetta, Saverio and Barozzi, Serena and Magini, Pamela and Bozzi, Valeria and Dezzani, Luca and Di Stazio, Mariateresa and Ferraro, Marcella and Perini, Giovanni and Seri, Marco and Balduini, Carlo L} }