Myotonic dystrophy: linkage with apolipoprotein E and estimation of the gene carrier status with genetic markers.

The genes for myotonic dystrophy (MD) and for apolipoprotein E (ApoE) belong to a chromosome 19 synthenic group of markers. A familial linkage analysis between MD and ApoE was performed using the J Ott LIPED program (IBM PC/XT, April 1984) to estimate the genetic distance between these 2 genes. Of a total of 136 individuals in 11 MD families, 81 were confirmed to be affected by the disease and 41 were asymptomatic. ApoE phenotypes were determined in 115 of these 122 individuals. No recombinant was observed out of 74 meioses which were informatives for both MD and the ApoE isoproteins. A global maximal lod score Z of 19.00 was obtained at the recombination fraction theta = 0. The upper theta value at the confidence interval corresponding to the peak lod score (Z max) - 1 was 0.03. This suggests that the loci for MD and ApoE are at a distance of 0 to 0.03 Morgan. Since ApoE and apolipoprotein C2 (ApoC2) have been shown by others to be about 40 kb apart, our data are therefore consistent with the distance estimate of 0.02 Morgan reported between MD and ApoC2. The D19S19 (LDR152) polymorphic DNA sequence is also tightly linked to MD on chromosome 19. The segregation of ApoE isoproteins and of ApoC2 and D19S19 DNA polymorphism was utilized for evaluating the probability for individuals at risk of inheriting the disease gene in MD families. Data are presented on 3 families to emphasize the usefulness of genetic markers to estimate the MD gene carrier status of asymptomatic individuals and also for those presenting a partial syndrome. The limitations of such approach are also discussed.