<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bottega, Roberta</style></author><author><style face="normal" font="default" size="100%">Nicchia, Elena</style></author><author><style face="normal" font="default" size="100%">Cappelli, Enrico</style></author><author><style face="normal" font="default" size="100%">Ravera, Silvia</style></author><author><style face="normal" font="default" size="100%">De Rocco, Daniela</style></author><author><style face="normal" font="default" size="100%">Faleschini, Michela</style></author><author><style face="normal" font="default" size="100%">Corsolini, Fabio</style></author><author><style face="normal" font="default" size="100%">Pierri, Filomena</style></author><author><style face="normal" font="default" size="100%">Calvillo, Michaela</style></author><author><style face="normal" font="default" size="100%">Russo, Giovanna</style></author><author><style face="normal" font="default" size="100%">Casazza, Gabriella</style></author><author><style face="normal" font="default" size="100%">Ramenghi, Ugo</style></author><author><style face="normal" font="default" size="100%">Farruggia, Piero</style></author><author><style face="normal" font="default" size="100%">Dufour, Carlo</style></author><author><style face="normal" font="default" size="100%">Savoia, Anna</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Hypomorphic FANCA mutations correlate with mild mitochondrial and clinical phenotype in Fanconi anemia.</style></title><secondary-title><style face="normal" font="default" size="100%">Haematologica</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Haematologica</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018 Mar</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">103</style></volume><pages><style face="normal" font="default" size="100%">417-426</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;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.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/29269525?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bottega, Roberta</style></author><author><style face="normal" font="default" size="100%">Nicchia, Elena</style></author><author><style face="normal" font="default" size="100%">Alfano, Caterina</style></author><author><style face="normal" font="default" size="100%">Glembotsky, Ana C</style></author><author><style face="normal" font="default" size="100%">Pastore, Annalisa</style></author><author><style face="normal" font="default" size="100%">Bertaggia-Calderara, Debora</style></author><author><style face="normal" font="default" size="100%">Bisig, Bettina</style></author><author><style face="normal" font="default" size="100%">Duchosal, Michel A</style></author><author><style face="normal" font="default" size="100%">Arbesú, Guillermo</style></author><author><style face="normal" font="default" size="100%">Alberio, Lorenzo</style></author><author><style face="normal" font="default" size="100%">Heller, Paula G</style></author><author><style face="normal" font="default" size="100%">Savoia, Anna</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Gray platelet syndrome: Novel mutations of the NBEAL2 gene.</style></title><secondary-title><style face="normal" font="default" size="100%">Am J Hematol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Am. J. Hematol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Alleles</style></keyword><keyword><style  face="normal" font="default" size="100%">Blood Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Frequency</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Gray Platelet Syndrome</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Platelet Aggregation</style></keyword><keyword><style  face="normal" font="default" size="100%">Platelet Count</style></keyword><keyword><style  face="normal" font="default" size="100%">Platelet Membrane Glycoproteins</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2017 02</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">92</style></volume><pages><style face="normal" font="default" size="100%">E20-E22</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><issue><style face="normal" font="default" size="100%">2</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/27870194?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Nicchia, Elena</style></author><author><style face="normal" font="default" size="100%">Benedicenti, Francesco</style></author><author><style face="normal" font="default" size="100%">Rocco, Daniela De</style></author><author><style face="normal" font="default" size="100%">Greco, Chiara</style></author><author><style face="normal" font="default" size="100%">Bottega, Roberta</style></author><author><style face="normal" font="default" size="100%">Inzana, Francesca</style></author><author><style face="normal" font="default" size="100%">Faleschini, Michela</style></author><author><style face="normal" font="default" size="100%">Bonin, Serena</style></author><author><style face="normal" font="default" size="100%">Cappelli, Enrico</style></author><author><style face="normal" font="default" size="100%">Mogni, Massimo</style></author><author><style face="normal" font="default" size="100%">Stanzial, Franco</style></author><author><style face="normal" font="default" size="100%">Svahn, Johanna</style></author><author><style face="normal" font="default" size="100%">Dufour, Carlo</style></author><author><style face="normal" font="default" size="100%">Savoia, Anna</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Clinical aspects of Fanconi anemia individuals with the same mutation of FANCF identified by next generation sequencing.</style></title><secondary-title><style face="normal" font="default" size="100%">Birth Defects Res A Clin Mol Teratol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Birth Defects Res. Part A Clin. Mol. Teratol.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2015 Dec</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">103</style></volume><pages><style face="normal" font="default" size="100%">1003-1010</style></pages><language><style face="normal" font="default" size="100%">ENG</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Fanconi anemia (FA) is a rare genetic disease characterized by congenital malformations, aplastic anemia and increased risk of developing malignancies. FA is genetically heterogeneous as it is caused by at least 17 different genes. Among these, FANCA, FANCC, and FANCG account for approximately 85% of the patients whereas the remaining genes are mutated in only a small percentage of cases. For this reason, the molecular diagnostic process is complex and not always extended to all the FA genes, preventing the characterization of individuals belonging to rare groups.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;The FA genes were analyzed using a next generation sequencing approach in two unrelated families.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;The analysis identified the same, c.484_485del, homozygous mutation of FANCF in both families. A careful examination of three electively aborted fetuses in one family and one affected girl in the other indicated an association of the FANCF loss-of-function mutation with a severe phenotype characterized by multiple malformations.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSION: &lt;/b&gt;The systematic use of next generation sequencing will allow the recognition of individuals from rare complementation groups, a better definition of their clinical phenotypes, and consequently, an appropriate genetic counseling. Birth Defects Research (Part A) 103:1003-1010, 2015. © 2015 Wiley Periodicals, Inc.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">12</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/26033879?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">De Rocco, Daniela</style></author><author><style face="normal" font="default" size="100%">Bottega, Roberta</style></author><author><style face="normal" font="default" size="100%">Cappelli, Enrico</style></author><author><style face="normal" font="default" size="100%">Cavani, Simona</style></author><author><style face="normal" font="default" size="100%">Criscuolo, Maria</style></author><author><style face="normal" font="default" size="100%">Nicchia, Elena</style></author><author><style face="normal" font="default" size="100%">Corsolini, Fabio</style></author><author><style face="normal" font="default" size="100%">Greco, Chiara</style></author><author><style face="normal" font="default" size="100%">Borriello, Adriana</style></author><author><style face="normal" font="default" size="100%">Svahn, Johanna</style></author><author><style face="normal" font="default" size="100%">Pillon, Marta</style></author><author><style face="normal" font="default" size="100%">Mecucci, Cristina</style></author><author><style face="normal" font="default" size="100%">Casazza, Gabriella</style></author><author><style face="normal" font="default" size="100%">Verzegnassi, Federico</style></author><author><style face="normal" font="default" size="100%">Cugno, Chiara</style></author><author><style face="normal" font="default" size="100%">Locasciulli, Anna</style></author><author><style face="normal" font="default" size="100%">Farruggia, Piero</style></author><author><style face="normal" font="default" size="100%">Longoni, Daniela</style></author><author><style face="normal" font="default" size="100%">Ramenghi, Ugo</style></author><author><style face="normal" font="default" size="100%">Barberi, Walter</style></author><author><style face="normal" font="default" size="100%">Tucci, Fabio</style></author><author><style face="normal" font="default" size="100%">Perrotta, Silverio</style></author><author><style face="normal" font="default" size="100%">Grammatico, Paola</style></author><author><style face="normal" font="default" size="100%">Hanenberg, Helmut</style></author><author><style face="normal" font="default" size="100%">Della Ragione, Fulvio</style></author><author><style face="normal" font="default" size="100%">Dufour, Carlo</style></author><author><style face="normal" font="default" size="100%">Savoia, Anna</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology.</style></title><secondary-title><style face="normal" font="default" size="100%">Haematologica</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Haematologica</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Amino Acid Substitution</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line</style></keyword><keyword><style  face="normal" font="default" size="100%">Cohort Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Computational Biology</style></keyword><keyword><style  face="normal" font="default" size="100%">Databases, Nucleic Acid</style></keyword><keyword><style  face="normal" font="default" size="100%">Fanconi Anemia</style></keyword><keyword><style  face="normal" font="default" size="100%">Fanconi Anemia Complementation Group Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Founder Effect</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Italy</style></keyword><keyword><style  face="normal" font="default" size="100%">Mosaicism</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2014 Jun</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">99</style></volume><pages><style face="normal" font="default" size="100%">1022-31</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;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.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">6</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/24584348?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">De Rocco, Daniela</style></author><author><style face="normal" font="default" size="100%">Cerqua, Cristina</style></author><author><style face="normal" font="default" size="100%">Goffrini, Paola</style></author><author><style face="normal" font="default" size="100%">Russo, Giovanna</style></author><author><style face="normal" font="default" size="100%">Pastore, Annalisa</style></author><author><style face="normal" font="default" size="100%">Meloni, Francesca</style></author><author><style face="normal" font="default" size="100%">Nicchia, Elena</style></author><author><style face="normal" font="default" size="100%">Moraes, Carlos T</style></author><author><style face="normal" font="default" size="100%">Pecci, Alessandro</style></author><author><style face="normal" font="default" size="100%">Salviati, Leonardo</style></author><author><style face="normal" font="default" size="100%">Savoia, Anna</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Mutations of cytochrome c identified in patients with thrombocytopenia THC4 affect both apoptosis and cellular bioenergetics.</style></title><secondary-title><style face="normal" font="default" size="100%">Biochim Biophys Acta</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Biochim. Biophys. Acta</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Base Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Cells, Cultured</style></keyword><keyword><style  face="normal" font="default" size="100%">Child, Preschool</style></keyword><keyword><style  face="normal" font="default" size="100%">Cytochromes c</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Mutational Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Embryo, Mammalian</style></keyword><keyword><style  face="normal" font="default" size="100%">Energy Metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Family Health</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Fibroblasts</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Lung</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation, Missense</style></keyword><keyword><style  face="normal" font="default" size="100%">Oxygen Consumption</style></keyword><keyword><style  face="normal" font="default" size="100%">Pedigree</style></keyword><keyword><style  face="normal" font="default" size="100%">Saccharomyces cerevisiae</style></keyword><keyword><style  face="normal" font="default" size="100%">Sequence Homology, Amino Acid</style></keyword><keyword><style  face="normal" font="default" size="100%">Thrombocytopenia</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2014 Feb</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">1842</style></volume><pages><style face="normal" font="default" size="100%">269-74</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;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.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/24326104?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Pecci, Alessandro</style></author><author><style face="normal" font="default" size="100%">Klersy, Catherine</style></author><author><style face="normal" font="default" size="100%">Gresele, Paolo</style></author><author><style face="normal" font="default" size="100%">Lee, Kieran J D</style></author><author><style face="normal" font="default" size="100%">De Rocco, Daniela</style></author><author><style face="normal" font="default" size="100%">Bozzi, Valeria</style></author><author><style face="normal" font="default" size="100%">Russo, Giovanna</style></author><author><style face="normal" font="default" size="100%">Heller, Paula G</style></author><author><style face="normal" font="default" size="100%">Loffredo, Giuseppe</style></author><author><style face="normal" font="default" size="100%">Ballmaier, Matthias</style></author><author><style face="normal" font="default" size="100%">Fabris, Fabrizio</style></author><author><style face="normal" font="default" size="100%">Beggiato, Eloise</style></author><author><style face="normal" font="default" size="100%">Kahr, Walter H A</style></author><author><style face="normal" font="default" size="100%">Pujol-Moix, Núria</style></author><author><style face="normal" font="default" size="100%">Platokouki, Helen</style></author><author><style face="normal" font="default" size="100%">Van Geet, Christel</style></author><author><style face="normal" font="default" size="100%">Noris, Patrizia</style></author><author><style face="normal" font="default" size="100%">Yerram, Preethi</style></author><author><style face="normal" font="default" size="100%">Hermans, Cedric</style></author><author><style face="normal" font="default" size="100%">Gerber, Bernhard</style></author><author><style face="normal" font="default" size="100%">Economou, Marina</style></author><author><style face="normal" font="default" size="100%">De Groot, Marco</style></author><author><style face="normal" font="default" size="100%">Zieger, Barbara</style></author><author><style face="normal" font="default" size="100%">De Candia, Erica</style></author><author><style face="normal" font="default" size="100%">Fraticelli, Vincenzo</style></author><author><style face="normal" font="default" size="100%">Kersseboom, Rogier</style></author><author><style face="normal" font="default" size="100%">Piccoli, Giorgina B</style></author><author><style face="normal" font="default" size="100%">Zimmermann, Stefanie</style></author><author><style face="normal" font="default" size="100%">Fierro, Tiziana</style></author><author><style face="normal" font="default" size="100%">Glembotsky, Ana C</style></author><author><style face="normal" font="default" size="100%">Vianello, Fabrizio</style></author><author><style face="normal" font="default" size="100%">Zaninetti, Carlo</style></author><author><style face="normal" font="default" size="100%">Nicchia, Elena</style></author><author><style face="normal" font="default" size="100%">Güthner, Christiane</style></author><author><style face="normal" font="default" size="100%">Baronci, Carlo</style></author><author><style face="normal" font="default" size="100%">Seri, Marco</style></author><author><style face="normal" font="default" size="100%">Knight, Peter J</style></author><author><style face="normal" font="default" size="100%">Balduini, Carlo L</style></author><author><style face="normal" font="default" size="100%">Savoia, Anna</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">MYH9-related disease: a novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations.</style></title><secondary-title><style face="normal" font="default" size="100%">Hum Mutat</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Hum. Mutat.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Age of Onset</style></keyword><keyword><style  face="normal" font="default" size="100%">Amino Acid Substitution</style></keyword><keyword><style  face="normal" font="default" size="100%">Cataract</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Association Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Hearing Loss, Sensorineural</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Italy</style></keyword><keyword><style  face="normal" font="default" size="100%">Linear Models</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Motor Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Myosin Heavy Chains</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Risk Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">Thrombocytopenia</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2014</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2014 Feb</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">35</style></volume><pages><style face="normal" font="default" size="100%">236-47</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;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.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/24186861?dopt=Abstract</style></custom1></record></records></xml>