Population frequency of myotonic dystrophy: higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland

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

Evaluation of an Exercise Field Test Using Heart Rate Monitors to Assess Cardiorespiratory Fitness and Heart Rate Recovery in an Asymptomatic Population

PURPOSE:Measures of cardiorespiratory fitness (CRF) and heart rate recovery (HRR) can improve risk stratification for cardiovascular disease, but these measurements are rarely made in asymptomatic individuals due to cost. An exercise field test (EFT) to assess CRF and HRR would be an inexpensive method for cardiovascular disease risk assessment in large populations. This study assessed 1) the predictive accuracy of a 12-minute run/walk EFT for estimating CRF ([Formula: see text]) and 2) the accuracy of HRR measured after an EFT using a heart rate monitor (HRM) in an asymptomatic population. METHODS:Fifty subjects (48% women) ages 18-45 years completed a symptom-limited exercise tolerance test (ETT) (Bruce protocol) and an EFT on separate days. During the ETT, [Formula: see text] was measured by a metabolic cart, and heart rate was measured continuously by a HRM and a metabolic cart. RESULTS:EFT distance and sex independently predicted[Formula: see text]. The average absolute difference between observed and predicted [Formula: see text] was 0.26 ± 3.27 ml·kg-1·min-1 for our model compared to 7.55 ± 3.64 ml·kg-1·min-1 for the Cooper model. HRM HRR data were equivalent to respective metabolic cart values during the ETT. HRR at 1 minute post-exercise during ETT compared to the EFT had a moderate correlation (r=0.75, p<0.001). CONCLUSION:A more accurate model to estimate CRF from a 12-minute run/walk EFT was developed, and HRR can be measured using a HRM in an asymptomatic population outside of clinical settings