Relu Cocoș1, Florina Raicu1,2, Ovidiu Lucian Băjenaru3,4, Iulia Olaru3,5, Laura Dumitrescu3,5, Bogdan Ovidiu Popescu6,7,8. 1. Department of Medical Genetics, Carol Davila University of Medicine and Pharmacy, 37 Dionisie Lupu Str, 020021, Bucharest, Romania. 2. Francisc I. Rainer Anthropological Research Institute, Romanian Academy, 8 Eroii Sanitari Bld, 050474, Bucharest, Romania. 3. Department of Clinical Neurosciences, Colentina Hospital Neurology Division, Carol Davila University of Medicine and Pharmacy, 37 Dionisie Lupu Str, 020021, Bucharest, Romania. 4. Ana Aslan National Institute of Geriatrics and Gerontology, 9 Căldărușani Str, 011241, Bucharest, Romania. 5. Department of Neurology, Colentina Clinical Hospital, 19-21 Stefan cel Mare Str, 020125, Bucharest, Romania. 6. Department of Clinical Neurosciences, Colentina Hospital Neurology Division, Carol Davila University of Medicine and Pharmacy, 37 Dionisie Lupu Str, 020021, Bucharest, Romania. bogdan.popescu@umfcd.ro. 7. Department of Neurology, Colentina Clinical Hospital, 19-21 Stefan cel Mare Str, 020125, Bucharest, Romania. bogdan.popescu@umfcd.ro. 8. Laboratory of Ultrastructural Pathology, Victor Babeș National Institute of Pathology, 99-101 Splaiul Independentei Str, 050096, Bucharest, Romania. bogdan.popescu@umfcd.ro.
Abstract
BACKGROUND: Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating movement disorders. The etiopathogenesis is complex, both genetic and environmental factors playing a role, but remains elusive. The CACNA1B gene codes for the N-type neuronal voltage-gated calcium channels CaV2.2, which may play a role in the development of some IFD. METHODS: We analyzed samples from the GENDYS cohort for mutations in CACNA1B gene, using targeted next-generation sequencing (NGS). RESULTS: The GENDYS cohort consists of 120 people with adult-onset IFD (cervical dystonia 47.5%, blepharospasm 47.2%, others 8.3%). Of these, 35% had subsequent topographical extension. Average age at onset was 42 and average disease durations 8 years. Targeted NGS revealed a novel frameshift mutation c.2291AGG > A, in exon 19, and a previously reported variant, c.6834T > G, in exon 47. CONCLUSION: Our findings suggest that disease-causing mutations in CACNA1B gene may be involved in the development of some adult-onset IFD. To our knowledge, this is the first study that identified a disease-causing CACNA1B gene mutation in association with adult-onset IFD.
BACKGROUND: Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating movement disorders. The etiopathogenesis is complex, both genetic and environmental factors playing a role, but remains elusive. The CACNA1B gene codes for the N-type neuronal voltage-gated calcium channels CaV2.2, which may play a role in the development of some IFD. METHODS: We analyzed samples from the GENDYS cohort for mutations in CACNA1B gene, using targeted next-generation sequencing (NGS). RESULTS: The GENDYS cohort consists of 120 people with adult-onset IFD (cervical dystonia 47.5%, blepharospasm 47.2%, others 8.3%). Of these, 35% had subsequent topographical extension. Average age at onset was 42 and average disease durations 8 years. Targeted NGS revealed a novel frameshift mutation c.2291AGG > A, in exon 19, and a previously reported variant, c.6834T > G, in exon 47. CONCLUSION: Our findings suggest that disease-causing mutations in CACNA1B gene may be involved in the development of some adult-onset IFD. To our knowledge, this is the first study that identified a disease-causing CACNA1B gene mutation in association with adult-onset IFD.
Authors: Alberto Albanese; Kailash Bhatia; Susan B Bressman; Mahlon R Delong; Stanley Fahn; Victor S C Fung; Mark Hallett; Joseph Jankovic; Hyder A Jinnah; Christine Klein; Anthony E Lang; Jonathan W Mink; Jan K Teller Journal: Mov Disord Date: 2013-05-06 Impact factor: 10.338
Authors: Joseph T Glessner; Muredach P Reilly; Cecilia E Kim; Nagahide Takahashi; Anthony Albano; Cuiping Hou; Jonathan P Bradfield; Haitao Zhang; Patrick M A Sleiman; James H Flory; Marcin Imielinski; Edward C Frackelton; Rosetta Chiavacci; Kelly A Thomas; Maria Garris; Frederick G Otieno; Michael Davidson; Mark Weiser; Abraham Reichenberg; Kenneth L Davis; Joseph I Friedman; Thomas P Cappola; Kenneth B Margulies; Daniel J Rader; Struan F A Grant; Joseph D Buxbaum; Raquel E Gur; Hakon Hakonarson Journal: Proc Natl Acad Sci U S A Date: 2010-05-20 Impact factor: 11.205
Authors: David Curtis; Anna E Vine; Andrew McQuillin; Nicholas James Bass; Ana Pereira; Radhika Kandaswamy; Jacob Lawrence; Adebayo Anjorin; Khalid Choudhury; Susmita R Datta; Vinay Puri; Robert Krasucki; Jonathan Pimm; Srinivasa Thirumalai; Digby Quested; Hugh M D Gurling Journal: Psychiatr Genet Date: 2011-02 Impact factor: 2.458
Authors: Rosario Trifiletti; Herbert M Lachman; Olivia Manusama; Deyou Zheng; Alberto Spalice; Pietro Chiurazzi; Allan Schornagel; Andreea M Serban; Rogier van Wijck; Janet L Cunningham; Sigrid Swagemakers; Peter J van der Spek Journal: Sci Rep Date: 2022-06-30 Impact factor: 4.996