G2019S Mutation of Leucine-Rich Repeat Kinase 2 Is a Cause of Lewy Body Dementia in Patients With North African Ancestors.

Autor:	Segers K; Neurology Department.; Geriatrics Department, Brugmann Hospital., Benoit F; Geriatrics Department, Brugmann Hospital., Levy S; Geriatrics Department, Brugmann Hospital., Martinet V; Geriatrics Department., Schulz JG; Neurology department, Saint Pierre Hospital., Bertrand F; Neurology Department., De Bourgoing G; Neurology Department., Tatillo C; Neurology Department., Praet JP; Geriatrics Department., Vandernoot I; Genetics Department, Erasme Hospital., Desmyter L; Genetics Department, Erasme Hospital., Peyrassol X; Genetics Department, Erasme Hospital., Kehagias P; Genetics Department, Erasme Hospital., Smits G; Genetics Department, Erasme Hospital., Dumoulin B; Clinical Research Unit, Brugmann Hospital, Université Libre de Bruxelles, Brussels, Belgium., Besse-Hammer T; Clinical Research Unit, Brugmann Hospital, Université Libre de Bruxelles, Brussels, Belgium., Dachy B; Neurology Department., Surquin M; Geriatrics Department, Brugmann Hospital.
Jazyk:	angličtina
Zdroj:	Alzheimer disease and associated disorders [Alzheimer Dis Assoc Disord] 2024 Oct-Dec 01; Vol. 38 (4), pp. 328-331. Date of Electronic Publication: 2024 Aug 07.
DOI:	10.1097/WAD.0000000000000643
Abstrakt:	Background: Mutations in the LRRK2 gene are the most common genetic cause of Parkinson disease but are believed to play no significant role in Lewy body disease (LBD). Objectives: As the frequency of G2019S LRRK2 mutation is extremely high in North African patients with Parkinson disease, we postulate that the high prevalence of LBD in North Africa might be due to the same mutation because LBD and Parkinson disease share many clinical, pathological, and genetic features. Methods: We screened patients with LBD or prodromal LBD for the G2019S mutation of LRRK2. Results: A total of 162 patients were tested for the mutation, which was present in 5 of the 47 patients with North African ancestors. This is a much higher prevalence (10.6%) than in healthy North African subjects (1.45%) but lower than in North African patients with Parkinson disease (36% to 39%). Carriers tended to develop more often orthostatic hypotension and swallowing problems. Conclusions: Where previous studies in European and North American patients found no link between LRRK2 mutations and LBD, we found an LRRK2 mutation associated with Lewy body disease, namely the G2019S mutation that might be restricted to patients with North African ancestors. Our study illustrates the need to introduce ethnic diversity as stratifying factor in the analysis of genetic causes of neurodegenerative disorders. The current development of disease-modifying drugs modulating LRRK2 kinase activity could justify to screen North African patients with LBD for the G2019S LRRK2 mutation. Competing Interests: The authors declare no conflicts of interest. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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