The missing tau mutation: + 15 exon 10/intron 10 boundary of MAPT stem loop structure in an Irish family with FTDP-17

Abstract

WCN 2013 No: 2532 Topic: 2 — Movement Disorders The missing tau mutation: +15 exon 10/intron 10 boundary of MAPT stem loop structure in an Irish family with FTDP-17 R. Lonergan, A. McCarthy, S. O'Dowd, B. Magennis, E. Fallon, M. Spillantini, M. Hutton, T. Lynch. Neurology, Mater Misericordiae Hospital, Dublin, Ireland; Molecular Neurology, Addenbrooke's Hospital, Cambridge, UK; Eli Lilly and Company, London, UK Background: Up to 40% of families with autosomal dominant frontotemporal dementia with parkinsonism (AD FTDP-17) carry pathogenic 5′ splice site mutations in the Microtubule-Associated Protein Tau (MAPT) gene. Several stem-loop mutations of tau exon 10 were identified, but the +15 mutation remained elusive. Aim: We present a family with the ‘missing’ +15 mutation. Case: A 44 year old man developed progressive disinhibition, apathy and simultaneous amnestic syndrome. Neurological examination normal (primitive reflexes/disinhibition). Pedigree: autosomal dominant young-onset dementia. Investigations: MRI brain — moderate bitemporal atrophy; PET CT — low anterior temporal activity. CSF — raised protein: phosphorylated tau/beta-amyloid normal. Fluorescent sequencing analysis for familial tau variant: sequence variant c.915 + 15A N C, at exon 10/intron 10 boundary of MAPT gene. Identical variant in first cousin. Discussion: In 1998, Hutton described 5′ splice site mutations in tau, associated with FTDP-17, destabilising a stem-loop structure, causing alternate splicing of exon 10. The predicted +15 A N C mutation at intron 10 was ‘missing’ until now. In this unique family, the proband had profound short-term amnesia and behavioral change, suggesting atypical familial Alzheimer disease or atypical FTDP-17. Detection of novel +15 mutation clarified diagnosis of FTDP-17 and informed genetic counselling. Finding this mutation 14 years after prediction highlights value of pursuing complete family history to guide appropriate molecular genetic testing. doi:10.1016/j.jns.2013.07.549 Abstract — WCN 2013 No: 2483 Topic: 2 — Movement Disorders Orthostatic tremor responding to Rasagiline WCN 2013 No: 2483 Topic: 2 — Movement Disorders Orthostatic tremor responding to Rasagiline M. Yucel, H. Akgun, S. Tasdemir, S. Alay, O. Oz, E. Eroglu, S. Demirkaya. Department of Neurology, Kasimpasa Military Hospital, Istanbul, Turkey; Department of Neurology, Etimesgut Military Hospital, Ankara, Turkey; Department of Neurology, Gulhane Military Medical Academy, Ankara, Turkey Background: Orthostatic tremor is known as a lower extremity tremor occurring when standing. When a person stands, typical high frequency (13–18 Hz) tremor develops, and disappears with walking, sitting or continuous volatile leg movement. Objective: In this report we presented a patient with tremor on the lower limbs diagnosed with Parkinson's disease. Patients and methods: A 58-year-old female patient presented to our outpatient clinic with complaints of trembling in the body when standing, lasting for 1 year. The neurological examination revealed bradykinesia of the lower and upper right limbs, rigidity and rest tremor of the right hand and trembling of the lower limbs when standing. Results: The brain MRI and the routine nerve conduction studies were normal. The superficial electrode recordings of femoris, anterior tibialis, biceps femoris muscles documented a tremor of 13 Hz. The patient was diagnosed with Parkinson's disease accompanied by orthostatic tremor and was started 2 mg of Rasagiline. Significant improvement was noted. Conclusion: We found this case worth reporting because of the rare presentation of Parkinson's disease in the literature with orthostatic symptoms as a first sign. doi:10.1016/j.jns.2013.07.550 Abstract — WCN 2013 No: 2514 Topic: 2 — Movement Disorders Extrapontine myelinolysis presented with sudden-onset generalised chorea WCN 2013 No: 2514 Topic: 2 — Movement Disorders Extrapontine myelinolysis presented with sudden-onset generalised chorea D. Petrlenicova, M. Kucharik, M. Saling. 2nd Dept. of Neurology, Faculty of Medicine, Comenius University, University Hospital Bratislava, Bratislava,