Screening of the glucocerebrosidase (GBA) gene in South Africans of African ancestry with Parkinson's disease.

Autor: Mahungu AC; Faculty of Medicine and Health Sciences, Division of Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa., Anderson DG; University of the Witwatersrand Donald Gordon Medical Centre, Neurology, University of the Witwatersrand, Johannesburg, South Africa., Rossouw AC; Faculty of Health Sciences, Division of Neurology, Department of Medicine, Walter Sisulu University, East London, South Africa., van Coller R; Faculty of Health Sciences, School of Medicine, Department of Neurology, University of Pretoria, South Africa., Carr JA; Faculty of Medicine and Health Sciences, Division of Neurology, Stellenbosch University, Cape Town, South Africa., Ross OA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Clinical Genomics, Mayo Clinic College of Medicine, Jacksonville, FL, USA., Bardien S; Faculty of Medicine and Health Sciences, Division of Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa. Electronic address: sbardien@sun.ac.za.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2020 Apr; Vol. 88, pp. 156.e11-156.e14. Date of Electronic Publication: 2019 Dec 20.
DOI: 10.1016/j.neurobiolaging.2019.12.011
Abstrakt: Sequence variants in glucocerebrosidase (GBA) are a major genetic risk factor for Parkinson's disease (PD), and display ethnic-dependent frequencies, for example, variants such as p.N370S and 84insGG are common in Ashkenazi Jewish patients. Notably, there are limited studies on black patients from the African continent; hence, we conducted a study on 30 South African black PD patients. All 11 exons of GBA were screened using a nested PCR approach to avoid pseudogene contamination. We identified previously described Gaucher's disease-associated variants, p.R120W in one patient [age at onset (AAO) of 35 years], and p.R131L in another patient (AAO 30 years) and in her affected sibling (AAO 45 years). In addition, we found 3 previously identified [p.K(-27)R, p.T36del, and p.Q497*] and 2 novel (p.F216L and p.G478R) variants. Screening of ethnic-matched controls for the novel variants revealed that the allele frequency of p.F216L was 9.9%, whereas p.G478R was not found in the controls. Studies such as these are important and necessary to reveal the genetic architecture underlying PD in the understudied patients of African ancestry.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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