Genetic variants of GBA and GLA in a Turkish cohort of Parkinson's disease: A preliminary report.

The role of disrupted lysosomal mechanisms in the pathophysiology of Parkinson's disease (PD) is being increasingly recognized [ [1] Brockmann K. GBA-associated synucleinopathies: prime candidates for alpha-synuclein targeting compounds. Front. Cell Dev. Biol. 2020; 8https://doi.org/10.3389/FCELL.2020.562522 Crossref PubMed Google Scholar , [2] Robak L.A. Jansen I.E. van Rooij J. Uitterlinden A.G. Kraaij R. Jankovic J. Heutink P. Shulman J.M. Nalls M.A. Plagnol V. Hernandez D.G. Sharma M. Sheerin U.M. Saad M. Simón-Sánchez J. Schulte C. Lesage S. Sveinbjörnsdóttir S. Arepalli S. Barker R. Ben Y. Berendse H.W. Berg D. Bhatia K. de Bie R.M.A. Biffi A. Bloem B. Bochdanovits Z. Bonin M. Bras J.M. Brockmann K. Brooks J. Burn D.J. Majounie E. Charlesworth G. Lungu C. Chen H. Chinnery P.F. Chong S. Clarke C.E. Cookson M.R. Cooper J.M. Corvol J.C. Counsell C. Damier P. Dartigues J.F. Deloukas P. Deuschl G. Dexter D.T. van Dijk K.D. Dillman A. Durif F. Dürr A. Edkins S. Evans J.R. Foltynie T. Dong J. Gardner M. Gibbs J.R. Goate A. Gray E. Guerreiro R. Harris C. van Hilten J.J. Hofman A. Hollenbeck A. Holton J. Hu M. Huang X. Wurster I. Mätzler W. Hudson G. Hunt S.E. Huttenlocher J. Illig T. Jónsson P.V. Lambert J.C. Langford C. Lees A. Lichtner P. Limousin P. Lopez G. Lorenz D. Lungu C. McNeill A. Moorby C. Moore M. Morris H.R. Morrison K.E. Escott-Price V. Mudanohwo E. O’sullivan S.S. Pearson J. Perlmutter J.S. Pétursson H. Pollak P. Post B. Potter S. Ravina B. Revesz T. Riess O. Rivadeneira F. Rizzu P. Ryten M. Sawcer S. Schapira A. Scheffer H. Shaw K. Shoulson I. Shulman J. Sidransky E. Smith C. Spencer C.C.A. Stefánsson H. Bettella F. Stockton J.D. Strange A. Talbot K. Tanner C.M. Tashakkori-Ghanbaria A. Tison F. Trabzuni D. Traynor B.J. Uitterlinden A.G. Velseboer D. Vidailhet M. Walker R. van de Warrenburg B. Wickremaratchi M. Williams N. Williams-Gray C.H. Winder-Rhodes S. Stefánsson K. Martinez M. Wood N.W. Hardy J. Heutink P. Brice A. Gasser T. Singleton A.B. Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease. Brain. 2017; 140: 3191-3203https://doi.org/10.1093/BRAIN/AWX285 Crossref PubMed Scopus (0) Google Scholar ]. One well-known culprit associated with PD is the heterozygous pathological variants of the beta-glucocerebrosidase gene (GBA), which contribute to the accumulation of alpha-synuclein via several mechanisms [ [1] Brockmann K. GBA-associated synucleinopathies: prime candidates for alpha-synuclein targeting compounds. Front. Cell Dev. Biol. 2020; 8https://doi.org/10.3389/FCELL.2020.562522 Crossref PubMed Google Scholar , [3] Goker-Alpan O. Schiffmann R. LaMarca M.E. Nussbaum R.L. McInerney-Leo A. Sidransky E. Parkinsonism among Gaucher disease carriers. J. Med. Genet. 2004; 41: 937-940https://doi.org/10.1136/JMG.2004.024455 Crossref PubMed Scopus (0) Google Scholar ]. The prevalence and clinical associations of GBA in PD have been well described. Another lysosomal gene that may be related to PD is X-linked alpha-galactosidase (GLA). Investigations on the role of GLA in PD are relatively limited, hindering the understanding of the entire perspective of lysosomal mechanisms in the pathophysiology of PD [ [2] Robak L.A. Jansen I.E. van Rooij J. Uitterlinden A.G. Kraaij R. Jankovic J. Heutink P. Shulman J.M. Nalls M.A. Plagnol V. Hernandez D.G. Sharma M. Sheerin U.M. Saad M. Simón-Sánchez J. Schulte C. Lesage S. Sveinbjörnsdóttir S. Arepalli S. Barker R. Ben Y. Berendse H.W. Berg D. Bhatia K. de Bie R.M.A. Biffi A. Bloem B. Bochdanovits Z. Bonin M. Bras J.M. Brockmann K. Brooks J. Burn D.J. Majounie E. Charlesworth G. Lungu C. Chen H. Chinnery P.F. Chong S. Clarke C.E. Cookson M.R. Cooper J.M. Corvol J.C. Counsell C. Damier P. Dartigues J.F. Deloukas P. Deuschl G. Dexter D.T. van Dijk K.D. Dillman A. Durif F. Dürr A. Edkins S. Evans J.R. Foltynie T. Dong J. Gardner M. Gibbs J.R. Goate A. Gray E. Guerreiro R. Harris C. van Hilten J.J. Hofman A. Hollenbeck A. Holton J. Hu M. Huang X. Wurster I. Mätzler W. Hudson G. Hunt S.E. Huttenlocher J. Illig T. Jónsson P.V. Lambert J.C. Langford C. Lees A. Lichtner P. Limousin P. Lopez G. Lorenz D. Lungu C. McNeill A. Moorby C. Moore M. Morris H.R. Morrison K.E. Escott-Price V. Mudanohwo E. O’sullivan S.S. Pearson J. Perlmutter J.S. Pétursson H. Pollak P. Post B. Potter S. Ravina B. Revesz T. Riess O. Rivadeneira F. Rizzu P. Ryten M. Sawcer S. Schapira A. Scheffer H. Shaw K. Shoulson I. Shulman J. Sidransky E. Smith C. Spencer C.C.A. Stefánsson H. Bettella F. Stockton J.D. Strange A. Talbot K. Tanner C.M. Tashakkori-Ghanbaria A. Tison F. Trabzuni D. Traynor B.J. Uitterlinden A.G. Velseboer D. Vidailhet M. Walker R. van de Warrenburg B. Wickremaratchi M. Williams N. Williams-Gray C.H. Winder-Rhodes S. Stefánsson K. Martinez M. Wood N.W. Hardy J. Heutink P. Brice A. Gasser T. Singleton A.B. 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