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Intrafamilial and interfamilial heterogeneity of PINK1-associated Parkinson's disease in Sudan
Univ Hosp Bonn, Dept Neurol, Bonn, Germany.;Univ Khartoum, Fac Dent, Dept Basic Med Sci, Khartoum, Sudan.;Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan.;Univ Hosp Bonn, Dept Neurol, Sigmund Freud Str 25, D-53127 Bonn, Germany..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan.;Sudan Univ Sci & Technol, Fac Med, Dept Biochem, Khartoum, Sudan..
Sorbonne Univ, Paris Brain Inst, Inst Cerveau, ICM,Inserm,CNRS, Paris, France..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
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2023 (English)In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 111, article id 105401Article in journal (Refereed) Published
Abstract [en]

PINK1 is the second most predominant gene associated with autosomal recessive Parkinson's disease. Homo-zygous mutations in this gene are associated with an early onset of symptoms. Bradykinesia, tremors, and rigidity are common features, while dystonia, motor fluctuation, and non-motor symptoms occur in a lower percentage of cases and usually respond well to levodopa. We investigated 14 individuals with parkinsonism and eleven symptom-free siblings from three consanguineous Sudanese families, two of them multigenerational, using a custom gene panel screening 34 genes, 27 risk variants, and 8 candidate genes associated with parkinsonism. We found a known pathogenic nonsense PINK1 variant (NM_032409.3:c.1366C>T; p.(Gln456*)), a novel pathogenic single base duplication (NM_032409.3:c.1597dup; p.(Gln533Profs*29)), and another novel pathogenic insertion (NM_032409.3:c.1448_1449ins[1429_1443; TTGAG]; p.(Arg483Serfs*7)). All variants were homozygous and co -segregated in all affected family members. We also identified intrafamilial and interfamilial phenotypic het-erogeneity associated with PINK1 mutations in these Sudanese cases, possibly reflecting the nature of the Sudanese population that has a large effective population size, which suggests a higher possibility of novel findings in monogenic and polygenic diseases in Sudan.

Place, publisher, year, edition, pages
Elsevier, 2023. Vol. 111, article id 105401
Keywords [en]
Parkinson, Sudan, PINK1, Heterogeneity
National Category
Neurology Neurosciences Medical Genetics and Genomics
Identifiers
URN: urn:nbn:se:uu:diva-506571DOI: 10.1016/j.parkreldis.2023.105401ISI: 000999042900001PubMedID: 37150071OAI: oai:DiVA.org:uu-506571DiVA, id: diva2:1776975
Available from: 2023-06-28 Created: 2023-06-28 Last updated: 2025-02-10Bibliographically approved

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Eltom, Khalid

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