Alpha-synuclein A53T mutation is not frequent on a sample of Brazilian Parkinson’s disease patients

Longo, G.; Pinhel, Marcela Augusta Souza; Gregório, Michele Lima; Oliveira, Bruno Affonso Parenti de; Quinhoneiro, Driele Cristina Gomes; Tognola, Waldir Antônio; Oliveira, Fábio de Nazaré; Martins, Denise Poltronieri; Cezario, Sabrina Mayara; Sado, Caroline L.; Nakazone, Marcelo Arruda; Calastri, Maria Clara Jessica; Souza, Dorotéia Rossi Silva

doi:10.1590/0004-282x20150032

Cited by 5 publications

(1 citation statement)

References 29 publications

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“…This review assessed 3014 studies, of which 73 met the inclusion criteria 20,35–106 . The process detailing the step‐by‐step inclusion and exclusion criteria is summarized in the PRISMA flow diagram 107 shown in Figure S2.…”

Section: Resultsmentioning

confidence: 99%

Frequency of Hereditary and GBA1‐Related Parkinsonism in Latin America: A Systematic Review and Meta‐Analysis

Saffie Awad,

Teixeira‐dos‐Santos,

Santos‐Lobato

et al. 2023

Movement Disorders

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BackgroundIdentifying hereditary parkinsonism is valuable for diagnosis, genetic counseling, patient prioritization in trials, and studying the disease for personalized therapies. However, most studies were conducted in Europeans, and limited data exist on admixed populations like those from Latin America.ObjectivesThis study aims to assess the frequency and distribution of genetic parkinsonism in Latin America.MethodsWe conducted a systematic review and meta‐analysis of the frequency of parkinsonian syndromes associated with genetic pathogenic variants in Latin America. We defined hereditary parkinsonism as those caused by the genes outlined by the MDS Nomenclature of Genetic Movement Disorders and heterozygous carriers of GBA1 pathogenic variants. A systematic search was conducted in PubMed, Web of Science, Embase, and LILACS in August 2022. Researchers reviewed titles and abstracts, and disagreements were resolved by a third researcher. After this screening, five researchers reanalyzed the selection criteria and extracted information based on the full paper. The frequency for each parkinsonism‐related gene was determined by the presence of pathogenic/likely pathogenic variants among screened patients. Cochran's Q and I2 tests were used to quantify heterogeneity. Meta‐regression, publication bias tests, and sensitivity analysis regarding study quality were also used for LRRK2‐, PRKN‐, and GBA1‐related papers.ResultsWe included 73 studies involving 3014 screened studies from 16 countries. Among 7668 Latin American patients, pathogenic variants were found in 19 different genes. The frequency of the pathogenic variants in LRRK2 was 1.38% (95% confidence interval [CI]: 0.52–2.57), PRKN was 1.16% (95% CI: 0.08–3.05), and GBA1 was 4.17% (95% CI: 2.57–6.08). For all meta‐analysis, heterogeneity was high and publication bias tests were negative, except for PRKN, which was contradictory. Information on the number of pathogenic variants in the other genes is further presented in the text.ConclusionsThis study provides insights into hereditary and GBA1‐related parkinsonism in Latin America. Lower GBA1 frequencies compared to European/North American cohorts may result from limited access to gene sequencing. Further research is vital for regional prevalence understanding, enabling personalized care and therapies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Section: Resultsmentioning

confidence: 99%

Frequency of Hereditary and GBA1‐Related Parkinsonism in Latin America: A Systematic Review and Meta‐Analysis

Saffie Awad,

Teixeira‐dos‐Santos,

Santos‐Lobato

et al. 2023

Movement Disorders

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The heterozygous A53T mutation in the alpha-synuclein gene in a Chinese Han patient with Parkinson disease: case report and literature review

et al. 2016

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The missense mutation A53T of alpha-synuclein gene (SNCA) was reported to be a rare but definite cause of sporadic and familial Parkinson disease (PD). It seemed to be restricted geographically in Greece and Italy. We aimed to identify the SNCA mutations in a Chinese PD cohort. Ninety-one early onset PD patients or familial PD probands were collected consecutively for the screening of PD-related genes. The genetic analysis was carried out by target sequencing of the exons and the corresponding flanking regions of the PD-related genes using Illumina HiSeq 2000 sequencer and further confirmed by Sanger sequencing or restriction fragment length polymorphism. Dosage mutations of exons in these genes were carried out by multiple ligation-dependent probe amplification. Among the 91 patients, we found only one heterozygous mutation of SNCA A53T, in a 23-year-old male patient with negative family history. The [(11)C]-2β-carbomethoxy-3β-(4-fluorophenyl) tropan (CFT) PET and PD-related spatial covariance pattern (PDRP) via [(18)F]-fluorodeoxyglucos (FDG) PET confirmed a typical pattern of PD. After examining his parents, we found his mother was an asymptomatic carrier, with declined hand dexterity detected by quantitative motor tests. Reduced dopamine transporter uptake of his mother was identified by CFT PET, and abnormal PDRP pattern was found by FDG PET. Our investigation expanded the clinical and genetic spectrum of Chinese PD patients, and we suggested SNCA mutations to be screened in familial and early onset Chinese PD patients.

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Genetic predispositions of Parkinson’s disease revealed in patient-derived brain cells

Tran

Anastacio

Bardy

2020

npj Parkinsons Dis.

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Parkinson's disease (PD) is the second most prevalent neurological disorder and has been the focus of intense investigations to understand its etiology and progression, but it still lacks a cure. Modeling diseases of the central nervous system in vitro with human induced pluripotent stem cells (hiPSC) is still in its infancy but has the potential to expedite the discovery and validation of new treatments. Here, we discuss the interplay between genetic predispositions and midbrain neuronal impairments in people living with PD. We first summarize the prevalence of causal Parkinson's genes and risk factors reported in 74 epidemiological and genomic studies. We then present a meta-analysis of 385 hiPSC-derived neuronal lines from 67 recent independent original research articles, which point towards specific impairments in neurons from Parkinson's patients, within the context of genetic predispositions. Despite the heterogeneous nature of the disease, current iPSC models reveal converging molecular pathways underlying neurodegeneration in a range of familial and sporadic forms of Parkinson's disease. Altogether, consolidating our understanding of robust cellular phenotypes across genetic cohorts of Parkinson's patients may guide future personalized drug screens in preclinical research.

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Alpha-synuclein A53T mutation is not frequent on a sample of Brazilian Parkinson’s disease patients

Cited by 5 publications

References 29 publications

Frequency of Hereditary and GBA1‐Related Parkinsonism in Latin America: A Systematic Review and Meta‐Analysis

Frequency of Hereditary and GBA1‐Related Parkinsonism in Latin America: A Systematic Review and Meta‐Analysis

The heterozygous A53T mutation in the alpha-synuclein gene in a Chinese Han patient with Parkinson disease: case report and literature review

Genetic predispositions of Parkinson’s disease revealed in patient-derived brain cells

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