Increased diagnostic yield in complex dystonia through exome sequencing

التفاصيل البيبلوغرافية
العنوان: Increased diagnostic yield in complex dystonia through exome sequencing
المؤلفون: Jamel Chelly, Cécile Laroche, Aurélie Méneret, Pierre Burbaud, Emmanuelle Ollivier, Marie-Aude Spitz, Cyril Mignot, Matthieu Bereau, Laurence Lion-François, Christine Tranchant, Mathieu Anheim, Emmanuel Roze, Diane Doummar, Laura Cif, Gabrielle Rudolf, Romain Lefaucheur, Stéphanie Bannier, Thomas Wirth, Domitille Gras, Nathalie Drouot, Vincent Laugel, Patrick Nitschke, Ouhaid Lagha-Boukbiza, Boris Keren
المساهمون: Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
المصدر: Parkinsonism and Related Disorders
Parkinsonism and Related Disorders, Elsevier, 2020, 74, pp.50-56. ⟨10.1016/j.parkreldis.2020.04.003⟩
سنة النشر: 2019
مصطلحات موضوعية: 0301 basic medicine, Adult, Male, Movement disorders, [SDV]Life Sciences [q-bio], Bioinformatics, GNAO1, DNA sequencing, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Exome Sequencing, medicine, Humans, Genetic Testing, Age of Onset, Exome, Exome sequencing, Aged, Dystonia, business.industry, High-Throughput Nucleotide Sequencing, Infant, medicine.disease, Reelin Protein, 030104 developmental biology, Phenotype, Neurology, Dystonic Disorders, Child, Preschool, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, Age of onset, business, 030217 neurology & neurosurgery, ADCK3
الوصف: A strategy based on targeted gene panel sequencing identifies possibly pathogenic variants in fewer than 20% of cases in early-onset and familial form of dystonia. By using Whole Exome Sequencing (WES), we aimed to identify the missing genetic causes in dystonic patients without diagnosis despite gene panel sequencing.WES was applied to DNA samples from 32 patients with early-onset or familial dystonia investigated by sequencing of a 127 movement disorders-associated gene panel. Dystonia was described according to the familial history, body distribution, evolution pattern, age of onset, associated symptoms and associated movement disorders. Rate of diagnoses was evaluated for each clinical feature.We identified causative variants for 11 patients from 9 families in CTNNB1, SUCLG1, NUS1, CNTNAP1, KCNB1, RELN, GNAO1, HIBCH, ADCK3 genes, yielding an overall diagnostic rate of 34.4%. Diagnostic yield was higher in complex dystonia compared to non-complex dystonia (66.7%-5.9%; p 0.002), especially in patients showing intellectual disability compared to the patients without intellectual disability (87.5%-16.7%; p 0.002).Our approach suggests WES as an efficient tool to improve the diagnostic yield after gene panel sequencing in dystonia. Larger study are warranted to confirm a potential genetic overlap between neurodevelopmental diseases and dystonia.
تدمد: 1873-5126
1353-8020
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dcc14f89bb0d41a20da4b2ea71ed7ac2Test
https://pubmed.ncbi.nlm.nih.gov/32334381Test
حقوق: CLOSED
رقم الانضمام: edsair.doi.dedup.....dcc14f89bb0d41a20da4b2ea71ed7ac2
قاعدة البيانات: OpenAIRE