The LRRK2 I2012T, G2019S, and I2020T mutations are rare in Taiwanese patients with sporadic Parkinson's disease

Mutations in the gene Leucine-Rich Repeat Kinase 2 (LRRK2, PARK8) are a cause of Parkinson's disease (PD) [ 1 Paisan-Ruiz C. Jain S. Evans E.W. Gilks W.P. Simon J. van der Brug M. de Munain A.L. Aparicio S. Gil A.M. Khan N. Johnson J. Martinez J.R. Nicholl D. Carrera I.M. Pena A.S. de Silva R. Lees A. Marti-Masso J.F. Perez-Tur J. Wood N.W. Singleton A.B. Cloning of the gene containing mutations that cause PARK8-linked parkinson's disease. Neuron. 2004; 44: 595-600 Abstract Full Text Full Text PDF PubMed Scopus (1864) Google Scholar , 2 Zimprich A. Biskup S. Leitner P. Lichtner P. Farrer M. Lincoln S. Kachergus J. Hulihan M. Uitti R.J. Calne D.B. Stoessl A.J. Pfeiffer R.F. Patenge N. Carbajal I.C. Vieregge P. Asmus F. Muller-Myhsok B. Dickson D.W. Meitinger T. Strom T.M. Wszolek Z.K. Gasser T. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004; 44: 601-607 Abstract Full Text Full Text PDF PubMed Scopus (2246) Google Scholar ], and they might account for more than 10% of the families with autosomal dominant inheritance of this disease [ [2] Zimprich A. Biskup S. Leitner P. Lichtner P. Farrer M. Lincoln S. Kachergus J. Hulihan M. Uitti R.J. Calne D.B. Stoessl A.J. Pfeiffer R.F. Patenge N. Carbajal I.C. Vieregge P. Asmus F. Muller-Myhsok B. Dickson D.W. Meitinger T. Strom T.M. Wszolek Z.K. Gasser T. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004; 44: 601-607 Abstract Full Text Full Text PDF PubMed Scopus (2246) Google Scholar ]. Importantly, LRRK2 mutations are also found in apparently sporadic PD cases. One mutation, G2019S, appears to be particularly common in Caucasian populations, being found in ∼3–6% of probands with familial PD and in ∼1% of sporadic cases [ 3 Di Fonzo A. Rohe C.F. Ferreira J. Chien H.F. Vacca L. Stocchi F. Guedes L. Fabrizio E. Manfredi M. Vanacore N. Goldwurm S. Breedveld G. Sampaio C. Meco G. Barbosa E. Oostra B.A. Bonifati V. A frequent LRRK2 gene mutation associated with autosomal dominant parkinson's disease. Lancet. 2005; 365: 412-415 Abstract Full Text Full Text PDF PubMed Scopus (440) Google Scholar , 4 Gilks W.P. Abou-Sleiman P.M. Gandhi S. Jain S. Singleton A. Lees A.J. Shaw K. Bhatia K.P. Bonifati V. Quinn N.P. Lynch J. Healy D.G. Holton J.L. Revesz T. Wood N.W. A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet. 2005; 365: 415-416 Abstract Full Text Full Text PDF PubMed Scopus (626) Google Scholar , 5 Kachergus J. Mata I.F. Hulihan M. Taylor J.P. Lincoln S. Aasly J. Gibson J.M. Ross O.A. Lynch T. Wiley J. Payami H. Nutt J. Maraganore D.M. Czyzewski K. Styczynska M. Wszolek Z.K. Farrer M.J. Toft M. Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations. Am J Hum Genet. 2005; 76: 672-680 Abstract Full Text Full Text PDF PubMed Scopus (442) Google Scholar , 6 Lesage S. Leutenegger A.-L. Ibanez P. Janin S. Lohmann E. Durr A. Brice A. LRRK2 haplotype analyses in European and North African families with Parkinson's disease: a common founder for the G2019S mutation dating from the 13th century. Am J Hum Genet. 2005; 77: 330-332 Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar , 7 Goldwurm S, Di Fonzo A, Simons EJ, Rohé CF, Zini M, Canesi M, Tesei S, Zecchinelli A, Antonini A, Mariani C, Meucci N, Sacilotto G, Sironi F, Salani G, Ferreira J, Chien HF, Fabrizio E, Vanacore N, Dalla Libera A, Stocchi F, Diroma C, Lamberti P, Sampaio C, Meco G, Barbosa E, Bertoli-Avella AM, Breedveld GJ, Oostra BA, Pezzoli G, Bonifati V. The G6055A (G2019S) mutation in LRRK2 is frequent in both early- and late-onset Parkinson's disease and originates from a common ancestor. J Med Genet; in press. Google Scholar ]. Moreover, haplotype analysis strongly suggests the presence of a founder effect for the G2019S mutation [ 5 Kachergus J. Mata I.F. Hulihan M. Taylor J.P. Lincoln S. Aasly J. Gibson J.M. Ross O.A. Lynch T. Wiley J. Payami H. Nutt J. Maraganore D.M. Czyzewski K. Styczynska M. Wszolek Z.K. Farrer M.J. Toft M. Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations. Am J Hum Genet. 2005; 76: 672-680 Abstract Full Text Full Text PDF PubMed Scopus (442) Google Scholar , 6 Lesage S. Leutenegger A.-L. Ibanez P. Janin S. Lohmann E. Durr A. Brice A. LRRK2 haplotype analyses in European and North African families with Parkinson's disease: a common founder for the G2019S mutation dating from the 13th century. Am J Hum Genet. 2005; 77: 330-332 Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar , 7 Goldwurm S, Di Fonzo A, Simons EJ, Rohé CF, Zini M, Canesi M, Tesei S, Zecchinelli A, Antonini A, Mariani C, Meucci N, Sacilotto G, Sironi F, Salani G, Ferreira J, Chien HF, Fabrizio E, Vanacore N, Dalla Libera A, Stocchi F, Diroma C, Lamberti P, Sampaio C, Meco G, Barbosa E, Bertoli-Avella AM, Breedveld GJ, Oostra BA, Pezzoli G, Bonifati V. The G6055A (G2019S) mutation in LRRK2 is frequent in both early- and late-onset Parkinson's disease and originates from a common ancestor. J Med Genet; in press. Google Scholar ].