Germ line risk variants: beyond cancer

In this issue of Blood, Molteni et al address how often deleterious germ line variants are associated with unexplained cytopenias and bone marrow hypocellularity.(1) They determined the frequency of these alleles in 402 consecutive adults evaluated for cytopenias and age-adjusted hypoplastic bone marrows. The authors considered the mode of inheritance for each condition, such that single deleterious variants were considered causative for autosomal dominant conditions but 2 deleterious variants were required for autosomal recessive disorders. DNA variants were curated according to the criteria outlined by the American College of Medical Genetics and Genomics (ACMG), the Association of Molecular Pathology (AMP), and ClinGen, which require rigorous assessment of functional, case/segregation, population, and computational/predictive data for each variant.

Automated summary

The study aims to evaluate the frequency of deleterious germ line variants in cytopenias and bone marrow hypocellularity, and to determine the pathogenic causes and associated mutations based on the mode of inheritance and strict screening criteria.