The clinical utility of exome sequencing and extended bioinformatic analyses in adolescents and adults with a broad range of neurological phenotypes: an Australian perspective

Currently there is no secured ongoing funding in Australia for next generation sequencing (NGS) such as exome (ES) adult neurological disorders. Studies have focused on paediatric populations research or highly specialised settings, utilised standard NGS pipelines focusing only small insertions, deletions and single nucleotide variants, not explored impacts management detail.This prospective multi-site study performed ES an extended bioinformatics repeat expansion analysis pipeline, patients with broad phenotypes (ataxia, dementia, dystonia, spastic paraparesis, motor neuron disease, Parkinson's disease complex/not-otherwise-specified), symptom onset between 2 60 years. Genomic data was phenotype-driven, using virtual gene panels, reported according to American College of Medical Genetics Genomics guidelines.One-hundred-and-sixty (51% female) were included, median age 52 years (range 14–79) 9 symptoms. 34/160 (21%) received a genetic diagnosis. Highest diagnostic rates paraparesis (10/25, 40%), complex/not-otherwise-specified (10/38, 26%) ataxia (7/28, 25%) groups. Findings considered ‘possible/uncertain’ 21/160 patients. Repeat detection identified unexpected diagnosis Huntington ataxic patient negative ES. Impacts management, more precise tailored care, seen most diagnosed (23/34, 68%).ES novel pipepline had substantial yield patients, heterogeneous, complex, mainly adult-onset disorders real-world settings Australia, providing evidence complementary multiple, new technologies valuable tools.