Background and aims: It is often the case that the genetic background of a rare disease has been solved, but the testing of a clinical patient can be performed only through research projects. Translating a research-based test into diagnostic service may also appear laborious and costly. Based on our molecular research of the genetics of Sotos syndrome, we developed a clinical laboratory test that is both effective and relatively inexpensive.
Methods and results: Pilot testing was performed with samples of clinically diagnosed Sotos cases (n=13), and testing was continued with samples of patients who were suspected of having Sotos syndrome (n=161). The testing methods used were direct sequencing and multiplex ligation-dependent probe amplification. Sotos syndrome was a suitable example for test translation, because its genetic background was well established, and the demand for the test was expected to be fairly high. In the pilot phase, a mutation was detected in 12 out of 13 patients (92%), and in the second group, 49 out of 161 (30%) patients had a mutation in the NSD1 gene.
Conclusions: In Sotos syndrome, detecting the mutation is valuable for the patient/family, while the value of a negative result is less clear and other differential diagnostic diagnoses should be considered. For successful translation of the research-based test into routine diagnostics, intense collaboration between clinicians, researchers, and diagnostic laboratory personnel is essential.