NEXT GENERATION SEQUENCING AS A DIAGNOSTIC TOOL FOR MUSCLE DISEASES.

Genetic confirmation of rare muscle diseases has for long been a tough challenge, using a one-by-one gene Sanger sequencing approach. With the advent of next generation sequencing (NGS), genetic diagnostic work has been considerably facilitated, and several centers around the world have now set up "muscle gene panels" or whole-exome sequencing techniques to diagnose previously undiagnosed patients with myopathy and new cases with no clear phenotype pointing at one disease. The use of NGS has proved particularly fruitful in the diagnostic workup of patients with suspected hereditary myopathies, providing diagnostic yields of close to 50% in many cases, which is a far better yield than for other diseases. Experiences with NGS using "muscle gene panels" in unclassified presumed genetic myopathies will be elaborated on in the talk, and alsothe many limitations of the technique, which include; 1) false-negative results (what type of mutations doesn't NGS cover?), 2) false-positive results, 3) verification of candidate genes that are not certain pathogenic, 4) the experience of the clinician in interpreting results, 5) ethics of accidental findings (what does the patient/family want to know), and 6) what to do with negative results? [ABSTRACT FROM AUTHOR]