This study states that Genomic (whole-exome and whole-genome) sequencing assays have gained broad use in the clinical setting, enabling accurate etiologic diagnosis, disorder-specific counselling, prognostication, and personalization of management.1, 2 However, molecular diagnostic rates with genomic sequencing vary across testing indications,3 and may also differ substantially between patients with the same disease entity depending on individual phenotypic factors.4-7 There is a clinically and economically grounded need to identify patients who are more likely to carry pathogenic DNA variation detectable by genomic sequencing, and therefore would be more likely to benefit from such testing.8, 9 Recently, we took advantage of a very large collection of whole-exome sequencing (WES) data from patients with dystonia to isolate clinical variables significantly associated with diagnostic outcome; these included (i) an onset of dystonia before the age of 21 years, (ii) a manifestation of segmental or generalized dystonia, and (iii) a combination of dystonia with non-dystonic neurological features (other movement disorders and/or non-movement disorder-related symptoms).10 On the basis of the predictor variables, we developed a weighted seven-component, five-point-maximum score that allows quantification of the likelihood of arriving at a molecular diagnosis through the application of WES.
Reference:https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28614
