Your browser doesn't support javascript.
loading
Exome sequencing in 116 patients with inherited thrombocytopenia that remained of unknown origin after systematic phenotype-driven diagnostic workup.
Marconi, Caterina; Pecci, Alessandro; Palombo, Flavia; Melazzini, Federica; Bottega, Roberta; Nardi, Elena; Bozzi, Valeria; Faleschini, Michela; Barozzi, Serena; Giangregorio, Tania; Magini, Pamela; Balduini, Carlo L; Savoia, Anna; Seri, Marco; Noris, Patrizia; Pippucci, Tommaso.
Affiliation
  • Marconi C; Department of Medical and Surgical Science, University of Bologna, Bologna.
  • Pecci A; Department of Internal Medicine, University of Pavia, Pavia, Italy; Medicina Generale 1, IRCCS Policlinico San Matteo Foundation, Pavia.
  • Palombo F; Department of Medical and Surgical Science, University of Bologna, Bologna.
  • Melazzini F; Department of Internal Medicine, University of Pavia, Pavia, Italy; Medicina Generale 1, IRCCS Policlinico San Matteo Foundation, Pavia.
  • Bottega R; Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste.
  • Nardi E; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna.
  • Bozzi V; Medicina Generale 1, IRCCS Policlinico San Matteo Foundation, Pavia.
  • Faleschini M; Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste.
  • Barozzi S; Medicina Generale 1, IRCCS Policlinico San Matteo Foundation, Pavia.
  • Giangregorio T; Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste.
  • Magini P; Medical Genetics Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna.
  • Balduini CL; Department of Internal Medicine, University of Pavia, Pavia.
  • Savoia A; Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy; Department of Medical Sciences, University of Trieste, Trieste.
  • Seri M; Department of Medical and Surgical Science, University of Bologna, Bologna, Italy; Medical Genetics Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna. marco.seri@unibo.it.
  • Noris P; Department of Internal Medicine, University of Pavia, Pavia, Italy; Medicina Generale 1, IRCCS Policlinico San Matteo Foundation, Pavia.
  • Pippucci T; Medical Genetics Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna.
Haematologica ; 108(7): 1909-1919, 2023 Jul 01.
Article in En | MEDLINE | ID: mdl-36519321
ABSTRACT
Inherited thrombocytopenias (IT) are genetic diseases characterized by low platelet count, sometimes associated with congenital defects or a predisposition to develop additional conditions. Next-generation sequencing has substantially improved our knowledge of IT, with more than 40 genes identified so far, but obtaining a molecular diagnosis remains a challenge especially for patients with non-syndromic forms, having no clinical or functional phenotypes that raise suspicion about specific genes. We performed exome sequencing (ES) in a cohort of 116 IT patients (89 families), still undiagnosed after a previously validated phenotype-driven diagnostic algorithm including a targeted analysis of suspected genes. ES achieved a diagnostic yield of 36%, with a gain of 16% over the diagnostic algorithm. This can be explained by genetic heterogeneity and unspecific genotype-phenotype relationships that make the simultaneous analysis of all the genes, enabled by ES, the most reasonable strategy. Furthermore, ES disentangled situations that had been puzzling because of atypical inheritance, sex-related effects or false negative laboratory results. Finally, ES-based copy number variant analysis disclosed an unexpectedly high prevalence of RUNX1 deletions, predisposing to hematologic malignancies. Our findings demonstrate that ES, including copy number variant analysis, can substantially contribute to the diagnosis of IT and can solve diagnostic problems that would otherwise remain a challenge.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Thrombocytopenia / Genetic Testing Type of study: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: Haematologica Year: 2023 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Thrombocytopenia / Genetic Testing Type of study: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: Haematologica Year: 2023 Document type: Article