title: Translation of a research-based genetic test on a rare syndrome into clinical service testing, with sotos syndrome as an example.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland. pia.pohjola@utu.fi
authors.forename: Pia
authors.initials: P
authors.lastname: Pohjola
authors.forename: Maarit
authors.initials: M
authors.lastname: Peippo
authors.forename: Maila T
authors.initials: MT
authors.lastname: Penttinen
authors.forename: Klaus
authors.initials: K
authors.lastname: Elenius
authors.forename: Helena
authors.initials: H
authors.lastname: Kääriäinen
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D058495:Sotos Syndrome / Q000175:diagnosis* / Q000235:genetics*; D057170:Translational Research, Biomedical
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human