RELN rare variants in myoclonus-dystonia
| Autor: | Raoul C.M. Hennekam, Sandra M. A. van der Salm, Katja Ritz, Justus L. Groen, Martin A. Haagmans, Marina A. J. Tijssen, Frank Baas, Hamid Jalalzadeh, Aldo Jongejan, Aeilko H. Zwinderman, M. Mahdi Motazacker, Olaf R.F. Mook |
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| Přispěvatelé: | Movement Disorder (MD), Other departments, Graduate School, 02 Surgical specialisms, Epidemiology and Data Science, ACS - Amsterdam Cardiovascular Sciences, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Other Research, Human Genetics, APH - Amsterdam Public Health, ANS - Amsterdam Neuroscience, Genome Analysis |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Adolescent Cell Adhesion Molecules Neuronal DNA Mutational Analysis RELN Nerve Tissue Proteins Biology medicine.disease_cause Bioinformatics myoclonus-dystonia Cohort Studies Young Adult medicine Missense mutation Humans genetics Reelin Exome sequencing Aged Dystonia Genetics Family Health Mutation Extracellular Matrix Proteins Genetic heterogeneity Serine Endopeptidases Middle Aged Disease gene identification medicine.disease Magnetic Resonance Imaging Reelin Protein Neurology Dystonic Disorders biology.protein Female Neurology (clinical) medicine.symptom Myoclonus |
| Zdroj: | Movement Disorders, 30(3), 415-419. Wiley Movement disorders, 30(3), 415-419. John Wiley and Sons Inc. |
| ISSN: | 0885-3185 |
| Popis: | BACKGROUND: Myoclonus-dystonia (M-D) is a hyperkinetic movement disorder with predominant myoclonic symptoms combined with dystonia of the upper part of the body. A proportion of M-D cases are caused by mutations in the epsilon-sarcoglycan gene. In remaining M-D patients, no genetic factor has been established, indicating genetic heterogeneity.METHODS: Patients were included in a prospective clinical database and recruited from referral centers and general neurology clinics in The Netherlands. To investigate new genetic causal factors in M-D syndrome, we performed homozygosity mapping combined with exome sequencing in a three-generation M-D family and genetically screened 24 additional patients with M-D.RESULTS: We found co-segregation of the rare missense variant Thr1904Met in the RELN gene. By additional screening of an M-D cohort, we identified co-segregation of RELN variants in two families (Thr1904Met, Ile1217Met) and identified two sporadic RELN mutation carriers (Pro1703Arg, Leu411Ile). Taken together, five of 25 SGCE-negative M-D patients carried RELN rare missense variants.CONCLUSION: We propose that RELN mutations contribute to the genetic heterogeneity of M-D. Reelin is a large secreted glycoprotein that plays essential roles in the cytoarchitecture of laminated brain structures and modulation of synaptic transmission and plasticity. © 2015 International Parkinson and Movement Disorder Society. |
| Databáze: | OpenAIRE |
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