Marie Hervieu-Begue (France)
Dijon University Hospital NeurologyAuthor Of 1 Presentation
HIGH EFFICIENCY AND CLINICAL RELEVANCE OF EXOME SEQUENCING IN THE DAILY PRACTICE OF NEUROGENETICS
- Quentin H. THOMAS (France)
Abstract
Background and Aims:
Exome Sequencing's (ES) relevance as a diagnostic tool in a real-life practice with heterogeneous cohort of patients presenting for neurogenetic evaluation is still debated and has yet to be assessed. Here, we report a prospective study using clinical ES (cES) as a first-tier test or after a non-contributive diagnostic odyssey in various progressive neurological disorders, regardless of age at onset, familial history or clinical spectrum, assessing the efficiency and relevance of cES in the daily practice of Neurology and Genetic Departments.
Methods:
Sixty-seven probands with various progressive neurological disorders (cerebellar ataxias, neuromuscular disorders, spastic paraplegias, movement disorders and individuals with complex phenotypes labeled “other”) were recruited over a 4-year period regardless of their age, gender, familial history and clinical framework. Individuals could have had prior genetic tests as long as it was not cES. cES was performed in a proband-only (60/67) or trio (7/67) strategy depending on available samples and was analyzed with an in-house pipeline including software for CNV and mitochondrial-DNA variant detection.
Results:
In 29/67 individuals, cES identified clearly pathogenic variants leading to a 43% positive yield. When performed as a first-tier test, cES identified pathogenic variants for 53% of individuals (10/19). Difficult cases were solved including double diagnoses within a kindred or identification of a neurodegeneration with brain iron accumulation in a patient with encephalopathy of suspected mitochondrial origin.
Conclusions:
This study shows that cES is a powerful tool for the daily practice of neurogenetics offering an efficient (43%) and appropriate approach for clinically and genetically complex and heterogeneous disorders.