Genome and RNA sequencing boost neuromuscular diagnoses to 62% from 34% with exome sequencing alone.
Rhett G MarchantSamantha J BryenMelanie BahloAnita CairnsKatherine R ChaoAlastair CorbettMark R DavisVijay S GaneshRoula GhaouiKristi J JonesAndrew J KornbergMonkol LekChristina LiangDaniel G MacArthurEmily C OatesAnne O'Donnell-LuriaGina L O'GradyIkeoluwa A Osei-OwusuHaloom RafehiStephen W ReddelRichard H RoxburghMonique M RyanSarah A SandaraduraLiam W ScottElise ValkanasBen WeisburdHelen YoungFrances J EvessonLeigh B WaddellSandra T CooperPublished in: Annals of clinical and translational neurology (2024)
Our results emphasize thorough clinical phenotyping to enable deep scrutiny of all rare genetic variation in phenotypically consistent genes. Post-exome auxiliary investigations extended our diagnostic yield by 81% overall (34-62%). We present a diagnostic algorithm that details deployment of genomic and auxiliary investigations to obtain these diagnoses today most effectively. We hope this provides a practical guide for clinicians as they gain greater access to clinical genome and transcriptome sequencing.