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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
PINK1 mutations and parkinsonism
Neurology, Volume 71, No. 12, Year 2008
Notification
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Description
BACKGROUND: PINK1 loss-of-function causes recessive, early-onset parkinsonism. In Tunisia there is a high rate of consanguineous marriage but PINK1 carrier frequency and disease prevalence have yet to be assessed. OBJECTIVES: The frequency of PINK1 mutations in familial parkinsonism, community-based patients with idiopathic Parkinson disease (PD) (non-familial PD), and control subjects was determined. Demographic and clinical characteristics of individuals with PINK1 homozygous or heterozygous variants, or without PINK1 mutations, were compared. METHODS: A total of 92 kindreds (with 208 affected and 340 unaffected subjects), 240 nonfamilial PD, and 368 control participants were recruited from the Institut National de Neurologie, Tunis. Clinical examinations included Hoehn &Yahr, UPDRS, and Epworth scales. PINK1 sequencing and dosage analysis was performed in familial index patients, the variants identified screened in all subjects. Parkin and LRRK2 genes were also examined. RESULTS: Four PINK1 homozygous mutations, three novel (Q129X, Q129fsX157, G440E, and one previously reported; Q456X), segregate with parkinsonism in 46 individuals in 14 of 92 families (15%). Six of 240 patients with nonfamilial PD were found with either homozygous Q456X or Q129X (2.5%) substitutions. In patients with familial disease, PINK1 homozygotes were younger at disease onset (36 ± 12 years) than noncarriers (57 ± 15 years) and more often had an akinetic-rigid presentation at examination and slow progression. CONCLUSIONS: Segregation of PINK1 mutations with parkinsonism within families, and frequency estimates within population controls, suggested only four PINK1 mutations were pathogenic. Several PINK1 sequence variants are potentially benign and there was no evidence that PINK1 heterozygosity increases susceptibility to idiopathic Parkinson disease. Copyright © 2008 by AAN Enterprises, Inc.
Authors & Co-Authors
Ishihara-Paul, L.
United Kingdom, Brentford
Glaxosmithkline Plc.
Hulihan, Mary M.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Kachergus, Jennifer M.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Upmanyu, R.
United Kingdom, Brentford
Glaxosmithkline Plc.
Warren, Liling
United States, Philadelphia
Glaxosmithkline, Usa
Amouri, Rim
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Elango, Ramu
United Kingdom, Brentford
Glaxosmithkline Plc.
Prinjha, Rab K.
United Kingdom, Brentford
Glaxosmithkline Plc.
Soto, Alexandra I.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
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: 47
Authors: 19
Affiliations: 4
Identifiers
Doi:
10.1212/01.wnl.0000323812.40708.1f
ISSN:
00283878
e-ISSN:
1526632X
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study
Study Locations
Tunisia