MYOTONIC-DYSTROPHY GENE ANALYSIS IN AFFECTED ISRAELI FAMILIES

Myotonic dystrophy (DM) is an autosomal dominant disease with an estim ated incidence of 1:7,500 individuals. The clinical manifestations are variable and include muscle wasting and weakness, myotonia, intellect ual impairment, cardiac abnormalities, cataracts, and testicular atrop hy. Despite its phenotypic variability, the disease is genetically hom ogeneous, and a specific molecular defect has been located to chromoso me 19q13.3 and found to be associated with the expansion and instabili ty of trinucleotide (CTG) repeats. Whereas normal individuals have 5-3 6 CTG repeats, affected individuals have 50 to several thousands. Ther efore, DM can now be diagnosed accurately using molecular biology tech niques that allow detailed analysis and determination of the size of D NA in the unstable DM gene region. In this way even mildly affected pa tients can be identified. We used this method to study the DM gene in 11 affected Israeli families (39 individuals.) In most of the families , the unstable DNA sequence increased in size when transmitted to offs pring. In one of the families we found contraction of the CTG repeat i n a DM offspring of an affected male; and in another family a CTG repe at contraction occurred in three offspring of an affected female while in the fourth offspring there was CTG expansion. Southern blot analys is using BgII restriction provided the most accurate technical results . There was an obvious phenotype/genotype correlation between the size of the CTG repeat and severity of disease.