Validity and utility of a LRRK2 G2019S mutation test for the diagnosis of Parkinson's disease

被引:16
|
作者
Kay, Denise M.
Bird, Tom D.
Zabetian, Cyrus P.
Factor, Stewart A.
Samii, Ali
Higgins, Donald S.
Nutt, John
Roberts, John W.
Griffith, Alida
Leis, Berta C.
Montimurro, Jennifer S.
Philpott, Sean
Payami, Haydeh
机构
[1] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA
[2] Univ Washington, Sch Med, Ctr Geriatr Res Educ & Clin, VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA
[3] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA
[4] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA
[5] Albany Med Ctr, Parkinsons Dis & Movement Disorder Clin, Albany, NY USA
[6] Univ Washington, Parkinsons Dis Res Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA
[7] Univ Washington, Dept Neurol, Seattle, WA 98195 USA
[8] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA
[9] Virginia Mason Med Ctr, Seattle, WA 98101 USA
[10] Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA
[11] Alden March Bioeth Inst, Albany, NY USA
来源
GENETIC TESTING | 2006年 / 10卷 / 03期
关键词
D O I
10.1089/gte.2006.10.221
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The G2019S mutation in the LRRK2 gene, the most common known cause of Parkinson's disease (PD), will soon be widely available as a molecular clinical test for PD. The objective of this study was to assess performance characteristics of G2019S as a clinical test for PD in the setting of typical movement disorder clinics in the United States. Subjects included 1518 sequentially recruited PD patients from seven movement disorder clinics in the United States, and 1733 unaffected subjects. All 3251 subjects were genotyped for the G2019S mutation using a TaqMan assay, and mutations were verified by direct sequencing. Test validity estimates were calculated using standard methods. A total of 20/1518 patients and 1/1733 controls carried the G2019S mutation. Specificity was 99.9% (95% CI, 99.6-100%), sensitivity was 1.3% (0.8-2.1%), and the positive likelihood ratio was 22.8. A positive family history of PD increased the positive likelihood ratio to 82.5. Information on gender, age at disease onset, or age at testing did not improve test performance. The gene test was highly accurate in classifying mutation carriers as PD, but it performed poorly in predicting the phenotype of non-mutation carriers. A G2019S molecular test for PD would be highly specific, technically simple, and inexpensive. Test interpretation is straightforward when used for diagnosis of symptomatic individuals, but is more complex for risk assessment and predictive testing in asymptomatic individuals. Test results can have psychological, social, and economical ramifications; thus, proper counseling is essential.
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收藏
页码:221 / 227
页数:7
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