Intrafamilial and interfamilial heterogeneity of PINK1-associated Parkinson's disease in SudanUniv Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Sudan Univ Sci & Technol, Fac Med, Dept Biochem, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan.;Univ Khartoum, Fac Med, Dept Anat, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan.;Inst Psychiat & Neurosci Paris, 102 rue Sante, F-75014 Paris, France..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan..
Univ Khartoum, Sudan Neurosci Projects SNPs, Khartoum, Sudan.;Mayo Clin, Dept Pulm & Crit Care, Phoenix, AZ USA..
Princess Nourah bint Abdulrahman Univ, Coll Med, Dept Basic Sci, POB 84428, Riyadh 11671, Saudi Arabia..
Sorbonne Univ, Paris Brain Inst, Inst Cerveau, ICM,Inserm,CNRS, Paris, France..
Sorbonne Univ, Pitie Salpetriere Hosp, Assistance Publ Hop Paris, Paris Brain Inst,Dept Neurol,ICM,Inserm,CNRS, Paris, France..
Univ Khartoum, Soba Teaching Hosp, Dept Neurol, Khartoum, Sudan..
Univ Hosp Bonn, Dept Neurol, Bonn, Germany.;German Ctr Neurodegenerat Dis DZNE, Bonn, Germany.;Univ Hosp Bonn, Dept Neurol, Sigmund Freud Str 25, D-53127 Bonn, Germany..
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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
2023-06-282023-06-282025-02-10Bibliographically approved