Molecular evidence for non-penetrance in Best's disease

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.