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

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VOLEJNIKOVA Jana VOJTA Petr URBANKOVA Helena MOJZIKOVA Renata HORVATHOVA Monika HOCHOVA Ivana CERMAK Jaroslav BLATNÝ Jan SUKOVA Martina BUBANSKA Eva FEKETEOVA Jaroslava PROCHAZKOVA Daniela HORAKOVA Julia HAJDUCH Marian POSPISILOVA Dagmar

Rok publikování 2020
Druh Článek v odborném periodiku
Časopis / Zdroj Blood Cells, Molecules and Diseases
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www http://dx.doi.org/10.1016/j.bcmd.2019.102380
Doi http://dx.doi.org/10.1016/j.bcmd.2019.102380
Klíčová slova Cancer; Diamond-Blackfan anemia (DBA); Mutations; Registry; Ribosomal proteins (RP)
Popis Diamond-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 beneficial for detection of novel mutations in DBA due to its capacity to detect larger chromosomal aberrations. Despite the importance of genotype-phenotype correlation in DBA, phenotypic differences among family members harboring an identical mutation were observed.