Population frequency of myotonic dystrophy

Bjarne Udd (1) , Tiina Suominen (1) , Linda L. Bachinski (1) , Satu Auvinen (1) , Peter Hackman (1) , Keith A. Baggerly (1) , Corrado Angelini (1) , Leena Peltonen (1) , Ralf Krahe (1)

1 Neurology Department

Myotonic dystrophy is the most common adult-onset muscular dystrophy with an estimated prevalence of 1/8,000. There are two genetically distinct types, DM1 and DM2. DM2 is generally milder with more phenotypic variability than classic DM1. Our previous data on co-segregation of heterozygous recessive CLCN1 mutations in DM2 patients indicated a higher than expected DM2 prevalence. The aim of this study was to determine the DM2 and DM1 frequency in the general population, and to explore if the DM2 mutation functions as a modifier in other neuromuscular diseases, to account for unexplained phenotypic variability. We genotyped 5,535 Finnish individuals: 4,532 normal blood donors, 606 patients with various non-myotonic NMD, 221 tibial muscular dystrophy patients and their 176 healthy relatives for the DM2 and DM1 mutations. We also genotyped an Italian idiopathic non-myotonic proximal myopathy cohort (n=93) for the DM2 mutation. In 5,496 samples analyzed for DM2, we found three DM2 mutations and two premutations. In 5,511 samples analyzed for DM1, we found two DM1 mutations and two premutations. In the Italian cohort we identified one patient with a DM2 mutation. We conclude that the DM2 mutation frequency is significantly higher in the general population (1/1,830; p-value=0.0326) than previously estimated. The identification of DM2 mutations in NMD patients with clinical phenotypes not previously associated with DM2 is of particular interest and in accord with the high overall prevalence. Based on our results, DM2 appears more frequent than DM1, with most DM2 patients currently undiagnosed with symptoms frequently occurring in the elderly population.

Mots clés: myotonic dystrophy; mutation frequency; population

Bjarne Udd, Tiina Suominen, Linda L. Bachinski, Satu Auvinen, Peter Hackman, et al.. Population frequency of myotonic dystrophy. European Journal of Human Genetics, 2011, ⟨10.1038/ejhg.2011.23⟩. ⟨hal-00618486⟩