Whole-exome sequencing broadens the phenotypic spectrum of rare pediatric epilepsy: a retrospective study
| Autor: | A.M. Innes, David A. Dyment, J.S. Parboosingh, Dennis E. Bulman, Taila Hartley, Chandree L. Beaulieu, Mark A. Tarnopolsky, Stephen J. Mosca, Kym M. Boycott, Julien L. Marcadier, Martine Tétreault, P. Ferreira, Care Rare Canada, Jodi Warman Chardon, Jeremy Schwartzentruber, Jacek Majewski, Sara L. Sawyer |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Adolescent DNA Mutational Analysis Encephalopathy SYNGAP1 Bioinformatics 03 medical and health sciences Epilepsy 0302 clinical medicine Genetics medicine Humans Exome Genetic Predisposition to Disease Child Genetics (clinical) Exome sequencing Retrospective Studies 030304 developmental biology Brain Diseases 0303 health sciences business.industry Genetic heterogeneity Infant Newborn Infant Retrospective cohort study medicine.disease Pedigree 3. Good health Phenotype Child Preschool Mutation ASAH1 Female business 030217 neurology & neurosurgery Rare disease |
| Zdroj: | Clinical Genetics. 88:34-40 |
| ISSN: | 0009-9163 |
| DOI: | 10.1111/cge.12464 |
| Popis: | Whole-exome sequencing (WES) has transformed our ability to detect mutations causing rare diseases. FORGE (Finding Of Rare disease GEnes) and Care4Rare Canada are nation-wide projects focused on identifying disease genes using WES and translating this technology to patient care. Rare forms of epilepsy are well-suited for WES and we retrospectively selected FORGE and Care4Rare families with clinical descriptions that included childhood-onset epilepsy or seizures not part of a recognizable syndrome or an early-onset encephalopathy where standard-of-care investigations were unrevealing. Nine families met these criteria and a diagnosis was made in seven, and potentially eight, of the families. In the eight families we identified mutations in genes associated with known neurological and epilepsy disorders: ASAH1, FOLR1, GRIN2A (two families), SCN8A, SYNGAP1 and SYNJ1. A novel and rare mutation was identified in KCNQ2 and was likely responsible for the benign seizures segregating in the family though additional evidence would be required to be definitive. In retrospect, the clinical presentation of four of the patients was considered atypical, thereby broadening the phenotypic spectrum of these conditions. Given the extensive clinical and genetic heterogeneity associated with epilepsy, our findings suggest that WES may be considered when a specific gene is not immediately suspected as causal. |
| Databáze: | OpenAIRE |
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