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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
LRRK2 Gly2019Ser penetrance in Arab-Berber patients from Tunisia: a case-control genetic study
The Lancet Neurology, Volume 7, No. 7, Year 2008
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Description
Background: Several genes have been implicated in the pathogenesis of Parkinson's disease (PD). The aim of this study was to define the clinical symptoms and age-associated cumulative incidence of the most frequent mutation associated with PD, LRRK2 Gly2019Ser. Methods: 238 patients with sporadic PD and 371 unrelated control participants from the Arab-Berber population were screened at the Institut National de Neurologie, Tunis. Symptoms of PD were assessed using the Hoehn and Yahr scale, the unified Parkinson's disease rating scale, and the Epworth scale. Genotyping for LRRK2 6055G→A, which causes the Gly2019Ser mutation, was done in all participants, and the age-specific cumulative incidence of PD was calculated by Kaplan-Meier analysis. Findings: 30% of patients with PD in this case-control sample were carriers of LRRK2 Gly2019Ser. The age of onset of symptoms and the clinical presentation of patients with LRRK2 Gly2019Ser were similar to those of patients with idiopathic PD. Carriers of LRRK2 Gly2019Ser were 22·6 times (95% CI 10·2-50·1) more likely to be affected by PD than non-carriers. Tremor was the predominant symptom in LRRK2 Gly2019Ser carriers (92% [homozygotes] vs 75% [heterozygotes] vs 69% [non-carriers]; Cochran-Armitage trend test p=0·0587). Disease severity, response to treatment, and disease duration were similar among LRRK2 Gly2019Ser homozygotes, heterozygotes, and non-carriers (p=0·85). Disease penetrance in LRRK2 Gly2019Ser carriers ranged from less than 20% in those younger than 50 years to greater than 80% at 70 years. Interpretation: The LRRK2 Gly2019Ser mutation in patients with PD is a useful aid to diagnosis. LRRK2 Gly2019Ser penetrance can vary but in most carriers PD seems an inevitable consequence of ageing. LRRK2 Gly2019Ser considerably increases susceptibility to neuronal degeneration, although the process might be mediated by many triggers. By contrast, idiopathic PD is rare before 50 years and the prevalence only increases to 4% in the oldest members of the population. Funding: GlaxoSmithKline; National Institutes of Health; and Mayo Foundation. © 2008 Elsevier Ltd. All rights reserved.
Authors & Co-Authors
Hulihan, Mary M.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Ishihara-Paul, L.
United Kingdom, Brentford
Glaxosmithkline Plc.
Kachergus, Jennifer M.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Warren, Liling
United States, Philadelphia
Glaxosmithkline, Usa
Amouri, Rim
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Elango, Ramu
United Kingdom, Brentford
Glaxosmithkline Plc.
Prinjha, Rab K.
United Kingdom, Brentford
Glaxosmithkline Plc.
Upmanyu, R.
United Kingdom, Brentford
Glaxosmithkline Plc.
Kefi, Mounir
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Zouari, Mourad
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Ben Sassi, Samia
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Yahmed, Samia Ben
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
El Euch-Fayeche, Ghada
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Matthews, Paul McMahan
United Kingdom, Brentford
Glaxosmithkline Plc.
Middleton, Lefkos T.
United Kingdom, Brentford
Glaxosmithkline Plc.
Gibson, Rachel A.
United Kingdom, Brentford
Glaxosmithkline Plc.
Hentati, F. F.
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Farrer, Matthew J.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Statistics
Citations: 172
Authors: 18
Affiliations: 4
Identifiers
Doi:
10.1016/S1474-4422(08)70116-9
ISSN:
14744422
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study
Cohort Study
Case-Control Study
Study Locations
Tunisia