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Autosomal dominant Parkinson's disease: Incidence of mutations in LRRK2, SNCA, VPS35 and GBA genes in Brazil.
Neurosci Lett. 2016 Dec 02; 635:67-70.NL

Abstract

INTRODUCTION

Amongst Parkinson's disease (PD) genetic factors, mutations in LRRK2, SNCA, VPS35 and GBA genes are recognized causes of PD. Nonetheless, few genetic screenings have been conducted in families with a history of PD consistent with autosomal dominant inheritance (ADPD), and their relevance to the etiology of PD has been poorly explored in Latin American populations, such as the Brazilian one, with a high degree of admixture.

METHODS

In order to assess the contribution of specific mutations in LRRK2, SNCA, VPS35 and GBA genes to ADPD in Brazil, we conducted the first molecular evaluation in a cohort of 141 index cases from families with ADPD. Genomic DNA was isolated from peripheral blood or saliva, and the molecular analysis was performed by TaqMan allelic discrimination assays or bidirectional sequencing.

RESULTS

Heterozygous mutations in LRRK2 and GBA genes were identified in 10 (7.0%) probands, and all presented typical signs of classical PD. No mutations were found in SNCA or VPS35 genes.

CONCLUSION

Our findings in a representative series of index cases from families with ADPD emphasize the important contribution of LRRK2 G2019S and GBA (L444P and N370S) mutations to parkinsonism in Brazilian families. The absence of mutations in VPS35 and SNCA genes reveals that they are uncommon causes of PD in Brazil, corroborating previous studies that also failed to detect these genetic variants in PD patients from other populations. Recent discoveries of novel causative genes of autosomal dominant forms of PD expand the investigative possibilities and should be targeted on future studies.

Authors+Show Affiliations

Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.Brazil Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.Movement Disorders Section, Neurology Service, Pedro Ernesto University Hospital, State University of Rio de Janeiro, Rio de Janeiro, Brazil.Movement Disorders Unit, Division of Neurology, Hospital Antônio Pedro, Fluminense Federal University, Brazil.University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.Santa Casa da Misericórdia do Rio de Janeiro, Rio de Janeiro, Brazil.Institute of Neurology Deolindo Couto, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Federal Hospital of Servidores do Estado, Rio de Janeiro, Brazil.Neuroscience Core, Hospital Clinics, Federal University of Goiás, Brazil; Integrated Neurosciences Institute, Goiás, Brazil.University Hospital Getúlio Vargas, Federal University of Amazonas, Amazonas, Brazil.Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: pimentel@uerj.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27777137

Citation

Abreu, Gabriella de M., et al. "Autosomal Dominant Parkinson's Disease: Incidence of Mutations in LRRK2, SNCA, VPS35 and GBA Genes in Brazil." Neuroscience Letters, vol. 635, 2016, pp. 67-70.
Abreu GM, Valença DC, Campos M, et al. Autosomal dominant Parkinson's disease: Incidence of mutations in LRRK2, SNCA, VPS35 and GBA genes in Brazil. Neurosci Lett. 2016;635:67-70.
Abreu, G. M., Valença, D. C., Campos, M., da Silva, C. P., Pereira, J. S., Araujo Leite, M. A., Rosso, A. L., Nicaretta, D. H., Vasconcellos, L. F., da Silva, D. J., Della Coletta, M. V., Dos Santos, J. M., Gonçalves, A. P., Santos-Rebouças, C. B., & Pimentel, M. M. (2016). Autosomal dominant Parkinson's disease: Incidence of mutations in LRRK2, SNCA, VPS35 and GBA genes in Brazil. Neuroscience Letters, 635, 67-70. https://doi.org/10.1016/j.neulet.2016.10.040
Abreu GM, et al. Autosomal Dominant Parkinson's Disease: Incidence of Mutations in LRRK2, SNCA, VPS35 and GBA Genes in Brazil. Neurosci Lett. 2016 Dec 2;635:67-70. PubMed PMID: 27777137.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autosomal dominant Parkinson's disease: Incidence of mutations in LRRK2, SNCA, VPS35 and GBA genes in Brazil. AU - Abreu,Gabriella de M, AU - Valença,Débora Cristina T, AU - Campos,Mário,Júnior AU - da Silva,Camilla P, AU - Pereira,João S, AU - Araujo Leite,Marco A, AU - Rosso,Ana Lucia, AU - Nicaretta,Denise H, AU - Vasconcellos,Luiz Felipe R, AU - da Silva,Delson José, AU - Della Coletta,Marcus V, AU - Dos Santos,Jussara M, AU - Gonçalves,Andressa P, AU - Santos-Rebouças,Cíntia B, AU - Pimentel,Márcia M G, Y1 - 2016/10/21/ PY - 2016/08/15/received PY - 2016/10/19/revised PY - 2016/10/20/accepted PY - 2016/10/30/pubmed PY - 2017/8/16/medline PY - 2016/10/30/entrez KW - Autosomal dominant Parkinson’s disease KW - GBA KW - LRRK2 KW - Parkinson’s disease KW - SNCA KW - VPS35 SP - 67 EP - 70 JF - Neuroscience letters JO - Neurosci Lett VL - 635 N2 - INTRODUCTION: Amongst Parkinson's disease (PD) genetic factors, mutations in LRRK2, SNCA, VPS35 and GBA genes are recognized causes of PD. Nonetheless, few genetic screenings have been conducted in families with a history of PD consistent with autosomal dominant inheritance (ADPD), and their relevance to the etiology of PD has been poorly explored in Latin American populations, such as the Brazilian one, with a high degree of admixture. METHODS: In order to assess the contribution of specific mutations in LRRK2, SNCA, VPS35 and GBA genes to ADPD in Brazil, we conducted the first molecular evaluation in a cohort of 141 index cases from families with ADPD. Genomic DNA was isolated from peripheral blood or saliva, and the molecular analysis was performed by TaqMan allelic discrimination assays or bidirectional sequencing. RESULTS: Heterozygous mutations in LRRK2 and GBA genes were identified in 10 (7.0%) probands, and all presented typical signs of classical PD. No mutations were found in SNCA or VPS35 genes. CONCLUSION: Our findings in a representative series of index cases from families with ADPD emphasize the important contribution of LRRK2 G2019S and GBA (L444P and N370S) mutations to parkinsonism in Brazilian families. The absence of mutations in VPS35 and SNCA genes reveals that they are uncommon causes of PD in Brazil, corroborating previous studies that also failed to detect these genetic variants in PD patients from other populations. Recent discoveries of novel causative genes of autosomal dominant forms of PD expand the investigative possibilities and should be targeted on future studies. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/27777137/Autosomal_dominant_Parkinson's_disease:_Incidence_of_mutations_in_LRRK2_SNCA_VPS35_and_GBA_genes_in_Brazil_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(16)30793-5 DB - PRIME DP - Unbound Medicine ER -