RESUMEN
Next generation sequencing provides an important opportunity for improved diagnosis in epilepsy. To date, the majority of diagnostic genetic testing is conducted in the paediatric arena, while the utility of such testing is less well understood in adults with epilepsy. We conducted whole exome sequencing (WES) and copy number variant analyses in an Irish cohort of 101 people with epilepsy and co-morbid intellectual disability to compare the diagnostic yield of genomic testing between adult and paediatric patients. Variant interpretation followed American College of Medical Genetics and Genomics (ACMG) guidelines. We demonstrate that WES, in combination with array-comparative genomic hybridisation, provides a diagnostic rate of 27% in unrelated adult epilepsy patients and 42% in unrelated paediatric patients. We observe a 2.7% rate of ACMG-defined incidental findings. Our findings indicate that WES has similar utility in both adult and paediatric cohorts and is appropriate for diagnostic testing in both epilepsy patient groups.
Asunto(s)
Epilepsia/genética , Pruebas Genéticas/métodos , Discapacidad Intelectual/genética , Adolescente , Adulto , Niño , Preescolar , Comorbilidad , Hibridación Genómica Comparativa/métodos , Hibridación Genómica Comparativa/normas , Epilepsia/diagnóstico , Epilepsia/epidemiología , Femenino , Pruebas Genéticas/normas , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/epidemiología , Masculino , Persona de Mediana Edad , Mutación , Sensibilidad y Especificidad , Secuenciación del Exoma/métodos , Secuenciación del Exoma/normasRESUMEN
OBJECTIVES: Both clinical genomics and e-Health technology are changing the way medicine is being practiced. Although the basic clinical methodology of good medical care will remain unchanged, the combined power of genomics and electronic health records has the capability of enhancing, and in some cases transforming, the practice of medicine. This is particularly true in the care of patients with complex long-term medical conditions such as chronic refractory epilepsy, especially in those with related complex comorbidities including intellectual disability and psychiatric disease. METHODS: Herein we outline the development and integration of an epilepsy genomics module into a preexisting epilepsy electronic patient record (EPR) system. RESULTS: We describe how this EPR infrastructure is used to facilitate discussion at multidisciplinary clinical meetings around molecular diagnosis and resulting changes in management. SIGNIFICANCE: This work illustrates the role of eHealth technology in embedding genomics into the clinical pathway.
