Targeted Next Generation Sequencing and Diagnosis of Congenital Hemolytic Anemias: A Three Years Experience Monocentric Study

• DOI: 10.3389/fphys.2021.684569
• Publication Date: 2021-05-21T07:42:26Z
• Authors: Elisa Fermo; Cristina Vercellati; Anna Paola Marcello; Ebru Yilmaz Keskin; Silverio Perrotta; Anna Zaninoni; Valentina Brancal...; Alberto Zanella; Juri A. Giannotta; Wilma Barcellini; Paola Bianchi
• Keywords: Risk Stratification

Congenital hemolytic anemias (CHAs) are heterogeneous and rare disorders caused by alterations in structure, membrane transport, metabolism, or red blood cell production. The pathophysiology of these diseases, particular the rarest, is often poorly understood, easy-to-apply tools for diagnosis, clinical management, patient stratification still lacking. We report 3-years monocentric experience with a 43 genes targeted Next Generation Sequencing (t-NGS) panel diagnosis CHAs; 122 patients from 105 unrelated families were investigated results compared conventional laboratory pathway. Patients divided two groups: 1) cases diagnosed hematologic investigations to be confirmed at molecular level, 2) unexplained anemia after extensive investigation. overall sensitivity t-NGS was 74 35% groups 1 2, respectively. Inside this cohort we identified 26 new pathogenic variants functional evidence. implementation work-up increased number diagnoses anemia; cytoskeleton defects well detected tools, deserving atypical cases; Gardos channelopathy, some enzyme deficiencies, familial siterosterolemia, X-linked females other ultra-rare diseases definitely benefits approaches.