In Reply:

Dr Finkh’s comments support the importance of exome analysis in diagnosis rare diseases, which often have genetic causes. We wish to emphasize, however, that in the Translate-NAMSE Project, exome analysis is integrated in an interdisciplinary treatment concept at centers for rare diseases, with participation of different medical specialties, including obligatory participation of human genetics. The specialties are involved on a patient-specific basis and include the laborious work-up of the patients’ medical results as well as recommendations for continued care after a diagnosis has been made and therapeutic recommendations and access to clinical treatment studies (national and often international).

A total of 5652 persons with unknown diseases received healthcare in the study, a diagnosis was possible in 1682, and exome analysis enabled a diagnosis in 506 of these. We showed that interdisciplinary case conferences are not only crucial for defining a targeted indication for exome analysis—and therefore also contribute to avoiding unnecessary exome analysis—but are also able in a large number of patients (n=1176) to make an often non-genetic diagnosis from all medical specialties.

We are convinced that if care is not based on interdisciplinary case conferences the patients’ odyssey will continue, owing to the genetic variants that can often be interpreted in a clinically unequivocal way only with a great deal of effort, and because of the difficulty in finding specific treatment expertise. This will even be exacerbated by the diagnostic sequencing of the entire genome (for which the German legislature has created the prerequisites with the model project according to §64e). The information contained in the non-coding regions of the genome is far more difficult to interpret, and interdisciplinary expertise will be even more crucial in this setting.