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Lianna Ishihara, MPhil; Liling Warren, PhD; Rachel Gibson, PhD; Rim Amouri, PhD; Suzanne Lesage, PhD; Alexandra Dürr, MD, PhD; Meriem Tazir, MD; Zbigniew K. Wszolek, MD; Ryan J. Uitti, MD; William C. Nichols, PhD; Alida Griffith, MD; Nobutaka Hattori, MD, PhD; David Leppert, MD; Ray Watts, MD; Cyrus P. Zabetian, MD, MS; Tatiana M. Foroud, PhD; Matthew J. Farrer, PhD; Alexis Brice, MD; Lefkos Middleton, MD; Faycal Hentati, MD

Arch Neurol. 2006;63:1250-1254.

Background  The G2019S mutation is the most common pathogenic substitution in the leucine-rich repeat kinase 2 (LRRK2) gene, which has recently been identified in familial and sporadic Parkinson disease (PD).

Objectives  To report the clinical characteristics of PD patients with homozygous LRRK2 6055G>A (G2019S) mutations and to compare them with previously published descriptions of heterozygous patients.

Design  Descriptive clinical report from an international consortium of studies.

Subjects  Patients with familial PD and homozygous LRRK2 mutations included 23 Tunisians, 2 Algerians, 2 US patients, 1 Canadian, and 1 Moroccan.

Results  There were no observable differences between the homozygote and heterozygote phenotypes.

Conclusions  Parkinson disease related to LRRK2 is characterized by typical clinical features, and the similarities between patients with homozygous and heterozygous mutations do not support a gene dosage effect.

Author Affiliations: Department of Public Health and Primary Care, University of Cambridge, Cambridge, England (Ms Ishihara); Research and Development, GlaxoSmithKline, Greenford, England (Drs Warren, Gibson, Leppert, and Middleton); Service de Neurologie, Institut National de Neurologie, Tunis, Tunisia (Drs Amouri and Hentati); Neurology and Experimental Therapeutics, Institut National de la Santé et de la Récherche Médicale U679 (Drs Lesage, Dürr, and Brice), Département de Neurologie (Drs Lesage, Dürr, and Brice) and Département de Génétique, Cytogénétique et Embryologie (Drs Dürr and Brice), Groupe Hôpital de la Pitié-Salpêtrière, Assitance Publique-Hôpitaux de Paris (AP-HP), Faculté de Médecine, Université Pierre et Marie Curie (Drs Lesage, Dürr, and Brice), and Fédération de Neurologie, Centre Hospitalier Universitaire (CHU) Pitié-Salpêtrière, AP-HP (Drs Dürr and Brice), Paris, France; Service de Neurologie, CHU Mustapha, Algiers, Algeria (Dr Tazir); Departments of Neurology (Drs Wszolek and Uitti) and Neuroscience (Dr Farrer), Mayo Clinic Jacksonville, Jacksonville, Fla; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio (Dr Nichols); Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Wash (Dr Griffith); Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan (Dr Hattori); Department of Neurology, University of Alabama at Birmingham (Dr Watts); Department of Neurology, University of Washington School of Medicine (Dr Zabetian), and Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System (Dr Zabetian), Seattle; and Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis (Dr Foroud).

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