Czech and Slovak Diamond-Blackfan Anemia (DBA) Registry update: Clinical data and novel causative genetic lesions

Publication date: Available online 11 November 2019Source: Blood Cells, Molecules, and DiseasesAuthor(s): Jana Volejnikova, Petr Vojta, Helena Urbankova, Renata Mojzíkova, Monika Horvathova, Ivana Hochova, Jaroslav Cermak, Jan Blatny, Martina Sukova, Eva Bubanska, Jaroslava Feketeova, Daniela Prochazkova, Julia Horakova, Marian Hajduch, Dagmar PospisilovaAbstractDiamond-Blackfan anemia (DBA) is a rare congenital erythroid aplasia, underlied by haploinsufficient mutations in genes coding for ribosomal proteins (RP) in approximately 70% of cases. DBA is frequently associated with somatic malformations, endocrine dysfunction and with an increased predisposition to cancer.Here we present clinical and genetic characteristics of 62 patients from 52 families enrolled in the Czech and Slovak DBA Registry. Whole exome sequencing (WES) and array comparative genomic hybridization (aCGH) were employed to identify causative mutations in newly diagnosed patients and in cases with previously unrecognized molecular pathology.RP mutation detection rate was 81% (50/62 patients). This included 8 novel point mutations and 4 large deletions encompassing some of the RP genes. Malignant or predisposing condition developed in 8/62 patients (13%): myelodysplastic syndrome in 3 patients; breast cancer in 2 patients; colorectal cancer plus ocular tumor, diffuse large B-cell lymphoma and multiple myeloma each in one case. These patients exclusively harbored RPL5, RPL11 or RPS19 mutations.Array CGH is b...
Source: Blood Cells, Molecules, and Diseases - Category: Hematology Source Type: research