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Molecular evidence for non-penetrance in Best's disease.

ABSTRACT: The present study provides evidence for a possible case of non-penetrance in Best's disease. We have analysed the at risk members of a three generation family with an established history of Best's disease by ophthalmoscopic examination, electrophysiological tests, and genetic analysis. The clinical examination identified 10 affected and five unaffected persons in this family. Genetic linkage analysis strongly supports linkage of the disease locus to DNA microsatellite markers from proximal 11q. The genotyping data were used to construct the familial haplotype associated with Best's disease. One person was identified who has inherited the Best's disease haplotype from his affected mother. Fundus examination and electrophysiological tests have repeatedly been performed in this patient but failed to show any signs of the disease. Based on these findings we have jointly estimated the most likely order of the Best's disease locus relative to the closet flanking markers at various penetrance values. A maximum likelihood estimate for the heterozygote penetrance was reached for the locus order D11S903-Best's disease-PYGM at a penetrance value of 0.96.

SUBMITTER: Weber BH

PROVIDER: S-EPMC1049871 | biostudies-other | 1994 May

REPOSITORIES: biostudies-other

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Molecular evidence for non-penetrance in Best's disease.

Weber B H BH Walker D D Müller B B

Journal of medical genetics 19940501 5

The present study provides evidence for a possible case of non-penetrance in Best's disease. We have analysed the at risk members of a three generation family with an established history of Best's disease by ophthalmoscopic examination, electrophysiological tests, and genetic analysis. The clinical examination identified 10 affected and five unaffected persons in this family. Genetic linkage analysis strongly supports linkage of the disease locus to DNA microsatellite markers from proximal 11q. ...[more]

PMID: 8064817

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Project description:BackgroundThe penetrance of leucine rich repeat kinase 2 (LRRK2) mutations is incomplete and may be influenced by environmental and/or other genetic factors. Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to reduce inflammation and may lower Parkinson's disease (PD) risk, but their role in LRRK2-associated PD is unknown.ObjectivesThe objective of this study is to evaluate the association of regular NSAID use and LRRK2-associated PD.MethodsSymptomatic ("LRRK2-PD") and asymptomatic ("LRRK2-non-PD") participants with LRRK2 G2019S, R1441X, or I2020T variants (definitely pathogenic variant carriers) or G2385R or R1628P variants (risk variant carriers) from 2 international cohorts provided information on regular ibuprofen and/or aspirin use (≥2 pills/week for ≥6 months) prior to the index date (diagnosis date for PD, interview date for non-PD). Multivariate logistic regression was used to evaluate the relationship between regular NSAID use and PD for any NSAID, separately for ibuprofen and aspirin in all carriers and separately in pathogenic and risk variant groups.ResultsA total of 259 LRRK2-PD and 318 LRRK2-non-PD participants were enrolled. Regular NSAID use was associated with reduced odds of PD in the overall cohort (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.21-0.57) and in both pathogenic and risk variant carriers (ORPathogenic , 0.38; 95% CI, 0.21-0.67 and ORRiskVariant , 0.19; 95% CI, 0.04-0.99). Similar associations were observed for ibuprofen and aspirin separately (ORIbuprofen , 0.19; 95% CI, 0.07-0.50 and ORAspirin , 0.51; 95% CI, 0.28-0.91).ConclusionsRegular NSAID use may be associated with reduced penetrance in LRRK2-associated PD. The LRRK2 protein is involved in inflammatory pathways and appears to be modulated by regular anti-inflammatory use. Longitudinal observational and interventional studies of NSAID exposure and LRRK2-PD are needed to confirm this association. © 2020 International Parkinson and Movement Disorder Society.

Dataset Information

Molecular evidence for non-penetrance in Best's disease.

Publications

Molecular evidence for non-penetrance in Best's disease.

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