Correspondence (letter to the editor): Supplemental Human Genetics Point of View

In their review, Bochtler et al. (1) describe the importance of genetic predispositions for hematological neoplasias. From a human genetics perspective, we would like to add the following clinically relevant aspects.

We note that, in contrast to the authors’ statement, the German Gene Diagnostics Act (Gendiagnostikgesetz, GenDG) does not require genetic counseling for diagnostic genetic examinations. In order to avoid delays in the diagnosis, which is in part essential for therapy, diagnostic genetic examinations can be carried out with the patient’s written informed consent following appropriate information by a physician. Upon notification of the results, genetic counseling should be offered.

After identification of DNA variants in hematological neoplasms, DNA from fingernails is not suitable for demonstrating the constitutional origin of identified variants. In patients who have received hematopoietic stem cell transplantation, donor DNA has been detected in the genome of the recipient’s fingernails (2).

Only sequencing the coding genes and flanking intronic regions is not sufficient when screening for predisposing gene changes. Rather, sequencing must be supplemented by adequate investigations for larger copy number changes in order to detect causative constitutional deletions or duplications, as recommended for RUNX1, for example (3).

In addition, genetic studies should also take into account relevant, deeply intronic regions (for example, in GATA2) or the possibility of revertant somatic mosaicism (for example, in SAMD9 / SAMD9L).

In contrast to the authors’ statement, the risk of developing breast cancer for female carriers of Fanconi anemia, for instance women who have heterozygous BRCA2 or PALB2 variants, can be increased significantly higher than threefold (4).

In summary, the challenges that were excellently described by Bochtler et al. show the importance of interdisciplinary cooperation. This cooperation would support early identification of a genetic predisposition for hematological neoplasms in patients, as well as future improvements in the diagnosis and care of those affected.