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From Cincinnati Children’s Hospital Medical Center (W.C.N., D.K.K., M.W.P., V.E.E., K.A.C.), OH; University of Cincinnati School of Medicine (W.C.N.), OH; Indiana University Medical Center (N.P., C.A.H., J.W., T.F.), Indianapolis; University of Rochester (A.R.), NY; and University of Tennessee Health Science Center (R.F.P.), Memphis.
Address correspondence and reprint requests to Dr. William C. Nichols, Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 bill.nichols{at}cchmc.org
Objective: A recent study reported that mutations in a gene on chromosome 2q36-37, GIGYF2, result in Parkinson disease (PD). We have previously reported linkage to this chromosomal region in a sample of multiplex PD families, with the strongest evidence of linkage obtained using the subset of the sample having the strongest family history of disease and meeting the strictest diagnostic criteria. We have tested whether mutations in GIGYF2 may account for the previously observed linkage finding.
Methods: We sequenced the GIGYF2 coding region in 96 unrelated patients with PD used in our original study that contributed to the chromosome 2q36-37 linkage signal. Subsequently, we genotyped the entire sample of 566 multiplex PD kindreds as well as 1,447 controls to test whether variants in GIGYF2 are causative or increase susceptibility for PD.
Results: We detected three novel variants as well as one of the previously reported seven variants in a total of five multiple PD families; however, there was no consistent evidence that these variants segregated with PD in these families. We also did not find a significant increase in risk for PD among those inheriting variants in GIGYF2 (p = 0.28).
Conclusions: We believe that variation in a gene other than GIGYF2 accounts for the previously reported linkage finding on chromosome 2q36-37.
GDS = Geriatric Depression Scale; MMSE = Mini-Mental State Examination; NCRAD = National Cell Repository for Alzheimer’s Disease; PD = Parkinson disease; PSG = Parkinson Study Group; UPDRS = Unified Parkinson’s Disease Rating Scale.
Supplemental data at www.neurology.org
Editorial, page 1882
e-Pub ahead of print on March 11, 2009, at www.neurology.org.
*The Parkinson Study Group–PROGENI Investigators are listed in the appendix.
Supported by R01 NS37167, MO1 RR-00750. Control samples and clinical data were provided by the National Cell Repository for Alzheimer’s Disease (U24 AG021886) and the National Institute of Neurological Disorders and Stroke Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds).
Disclosure: The authors report no disclosures.
Medical Devices: 3730xl DNA Analyzer (Applied Biosystems, Foster City, CA).
Received July 8, 2008. Accepted in final form December 30, 2008.
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Neurology 2009 72: 1882-1883.
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