Abstract
Myotonic dystrophy (DM) is the most common adult-onset muscular dystrophy with an estimated prevalence of 1/8000. There are two genetically distinct types, DM1 and DM2. DM2 is generally milder with more phenotypic variability than the 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 whether the DM2 mutation functions as a modifier in other neuromuscular diseases (NMD) to account for unexplained phenotypic variability. We genotyped 5535 Finnish individuals: 4532 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 5496 samples analyzed for DM2, we found three DM2 mutations and two premutations. In 5511 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 (1/1830; 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 is in accord with the high overall prevalence. On the basis of our results, DM2 appears more frequent than DM1, with most DM2 patients currently undiagnosed with symptoms frequently occurring in the elderly population.
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Acknowledgements
We acknowledge Tamer Ahmed for his technical assistance with DM2 and DM1 mutation analysis. We also acknowledge Merja Soininen and Satu Luhtasela for their assistance with sample preparations and logistics. TS was funded by the Finnish Cultural Foundation, Pirkanmaa Regional fund and the Pirkanmaa Hospital District research fund. CA was supported by the Telethon Genetic Biobank project GTB07001, the Eurobiobank project no. QLRI-CT-2002-02769 and the Cariparo grant. RK was supported by grants from the NIH (AR48171), the Muscular Dystrophy Association, USA and by the Kleberg Foundation. BU was supported by grants from the Vaasa Central Hospital district and Pirkanmaa Hospital district medical research funds and the Liv och Hälsa medical research foundation.
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Suominen, T., Bachinski, L., Auvinen, S. et al. Population frequency of myotonic dystrophy: higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland. Eur J Hum Genet 19, 776–782 (2011). https://doi.org/10.1038/ejhg.2011.23
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DOI: https://doi.org/10.1038/ejhg.2011.23
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