Novel and known ribosomal causes of Diamond-Blackfan anemia identified through comprehensive genomic characterization

Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome primarily caused by defects in ribosome biology. It is associated with physical anomalies and high risk of specific cancers. We performed comprehensive genomic analyses of 35 genetically uncharacterized DBA families participating in the National Cancer’s Institute’s DBA cohort (ClinicalTrials.gov Identifier: NCT00027274). Using whole exome sequencing, copy number variation and array comparative genomic hybridization, we discovered variants in two genes not previously associated with DBA, RPL18 and RPL35. These variants caused characteristic ribosome assembly defects consistent with the DBA biology. Overall, this combination of genomic methods led to the identification the causative variant in 72% of the cohort. Efforts are underway to identify the underlying genetic cause of DBA in the remaining families. (By Dr. Payal P. Khincha, http://jmg.bmj.com/content/early/2017/03/09/jmedgenet-2016-104346 )