BACKGROUND: Mutations in parkin are estimated to account for as much as 50% of familial Parkinson disease (PD) and 18% of sporadic PD. Single heterozygous mutations in parkin in both familial and sporadic cases may also increase susceptibility to PD. To our knowledge, all previous studies have been restricted to PD cases; this is the first study to systematically screen the parkin coding regions and exon deletions and duplications in controls. OBJECTIVE: To determine the frequency and spectrum of parkin variants in early-onset PD cases (aged < or =50 years) and controls participating in a familial aggregation study. PATIENTS AND METHODS: We sequenced the parkin gene in 101 cases and 105 controls. All cases and controls were also screened for exon deletions and duplications by semiquantitative multiplex polymerase chain reaction. RESULTS: Thirteen (12.9% [95% confidence interval, 7%-21%]) of the 101 cases had a previously described parkin mutation: 1 was homozygous, 11 were heterozygous, and 1 was a compound heterozygote. The mutations Arg42Pro (exon 2) and Arg275Trp (exon 7) were recurrent. The previously reported synonymous substitution Leu261Leu (c.884A>G) was identified in 4 (3.9%) of 101 cases and 2 (2%) of 105 controls (P = .44). Excluding the synonymous substitution Leu261Leu (heterozygotes), 10 (9.9% [95% confidence interval, 4.6%-17.5%]) carried mutations. CONCLUSIONS: The frequency of mutations among cases that were not selected based on family history of PD is similar to what has previously been reported in sporadic PD. The similar frequency of Leu261Leu in cases and controls suggests it is a normal variant rather than a disease-associated mutation. We confirmed that heterozygous parkin mutations may increase susceptibility for early-onset PD.
BACKGROUND: Mutations in parkin are estimated to account for as much as 50% of familial Parkinson disease (PD) and 18% of sporadic PD. Single heterozygous mutations in parkin in both familial and sporadic cases may also increase susceptibility to PD. To our knowledge, all previous studies have been restricted to PD cases; this is the first study to systematically screen the parkin coding regions and exon deletions and duplications in controls. OBJECTIVE: To determine the frequency and spectrum of parkin variants in early-onset PD cases (aged < or =50 years) and controls participating in a familial aggregation study. PATIENTS AND METHODS: We sequenced the parkin gene in 101 cases and 105 controls. All cases and controls were also screened for exon deletions and duplications by semiquantitative multiplex polymerase chain reaction. RESULTS: Thirteen (12.9% [95% confidence interval, 7%-21%]) of the 101 cases had a previously described parkin mutation: 1 was homozygous, 11 were heterozygous, and 1 was a compound heterozygote. The mutations Arg42Pro (exon 2) and Arg275Trp (exon 7) were recurrent. The previously reported synonymous substitution Leu261Leu (c.884A>G) was identified in 4 (3.9%) of 101 cases and 2 (2%) of 105 controls (P = .44). Excluding the synonymous substitution Leu261Leu (heterozygotes), 10 (9.9% [95% confidence interval, 4.6%-17.5%]) carried mutations. CONCLUSIONS: The frequency of mutations among cases that were not selected based on family history of PD is similar to what has previously been reported in sporadic PD. The similar frequency of Leu261Leu in cases and controls suggests it is a normal variant rather than a disease-associated mutation. We confirmed that heterozygous parkin mutations may increase susceptibility for early-onset PD.
Authors: Madeleine E Sharp; Elise Caccappolo; Helen Mejia-Santana; Ming-X Tang; Llency Rosado; Martha Orbe Reilly; Diana Ruiz; Elan D Louis; Cynthia Comella; Martha Nance; Susan Bressman; William K Scott; Caroline Tanner; Cheryl Waters; Stanley Fahn; Lucien Cote; Blair Ford; Michael Rezak; Kevin Novak; Joseph H Friedman; Ronald Pfeiffer; Haydeh Payami; Eric Molho; Stuart A Factor; John Nutt; Carmen Serrano; Maritza Arroyo; Michael W Pauciulo; William C Nichols; Lorraine N Clark; Roy N Alcalay; Karen S Marder Journal: Mov Disord Date: 2014-11-12 Impact factor: 10.338
Authors: D M Kay; C F Stevens; T H Hamza; J S Montimurro; C P Zabetian; S A Factor; A Samii; A Griffith; J W Roberts; E S Molho; D S Higgins; S Gancher; L Moses; S Zareparsi; P Poorkaj; T Bird; J Nutt; G D Schellenberg; H Payami Journal: Neurology Date: 2010-09-28 Impact factor: 9.910
Authors: Elise Caccappolo; Roy N Alcalay; Helen Mejia-Santana; Ming-X Tang; Brian Rakitin; Llency Rosado; Elan D Louis; Cynthia L Comella; Amy Colcher; Danna Jennings; Martha A Nance; Susan Bressman; William K Scott; Caroline M Tanner; Susan F Mickel; Howard F Andrews; Cheryl Waters; Stanley Fahn; Lucien J Cote; Steven Frucht; Blair Ford; Michael Rezak; Kevin Novak; Joseph H Friedman; Ronald F Pfeiffer; Laura Marsh; Brad Hiner; Andrew D Siderowf; Barbara M Ross; Miguel Verbitsky; Sergey Kisselev; Ruth Ottman; Lorraine N Clark; Karen S Marder Journal: J Int Neuropsychol Soc Date: 2010-11-24 Impact factor: 2.892
Authors: Roy N Alcalay; Helen Mejia-Santana; Ming X Tang; Brian Rakitin; Llency Rosado; Barbara Ross; Miguel Verbitsky; Sergey Kisselev; Elan D Louis; Cynthia L Comella; Amy Colcher; Danna Jennings; Martha A Nance; Susan Bressman; William K Scott; Caroline Tanner; Susan F Mickel; Howard F Andrews; Cheryl H Waters; Stanley Fahn; Lucien J Cote; Steven J Frucht; Blair Ford; Michael Rezak; Kevin Novak; Joseph H Friedman; Ronald Pfeiffer; Laura Marsh; Bradley Hiner; Andrew Siderowf; Ruth Ottman; Lorraine N Clark; Karen S Marder; Elise Caccappolo Journal: J Clin Exp Neuropsychol Date: 2010-02-24 Impact factor: 2.475
Authors: L N Clark; B M Ross; Y Wang; H Mejia-Santana; J Harris; E D Louis; L J Cote; H Andrews; S Fahn; C Waters; B Ford; S Frucht; R Ottman; K Marder Journal: Neurology Date: 2007-09-18 Impact factor: 9.910