Characteristics of myotonic dystrophy in Istria: molecular genetics approach--mutation analysis

Myotonic dystrophy (DM) is the most prevalent myopathy in adults. In Istria one of the highest prevalence rates of 18/100,000 has been reported. Two loci, the most prevalent 19q locus with mutations in the myotonin protein kinase gene and the second locus mapped to the 3q have been so far implicated in DM. The purpose of this study was to evaluate the molecular pathogenesis in the Istrian population by the analysis of (CTG) expansion in myotonin protein kinase gene. Additionally genotype--phenotype correlation was analysed, as well as the transmission of expanded trinucleotides through generations. We investigated 27 DM patients from the 10 families that were ascertained in Istria in our previous epidemiological study. Southern blot and polymerase chain reaction (PCR) techniques were used to evaluate the (CTG) expansion. In 9 of the 10 DM families an amplification was identified as the mechanism of mutation. A correlation between the size of the (CTG) expansion and phenotype was found. Among 10 parent-child transmission analysed, one reduction, 2 stable transmissions and 7 amplifications were observed, one through the affected father. The amplification of (CTG) in the myotonin protein kinase gene was identified in the majority of Istrian DM families. Direct mutation analysis is the method of choice for clinical and prenatal diagnosis of DM.