An Intronic Heterozygous SYNE2 Splice Site Mutation: A Rare Cause for Myalgia and hyperCKemia?

SYNE2 mutations have been associated with skeletal and cardiac muscle diseases, including Emery-Dreifuss muscular dystrophy (EDMD). Here, we present a 70-year-old male patient with muscle pain and elevated serum creatine kinase levels in whom whole-exome sequencing revealed a novel heterozygous SYNE2 splice site mutation (NM_182914.3:c.15306+2T>G). This mutation is likely to result in the loss of the donor splice site in intron 82. While a diagnostic muscle biopsy showed unspecific myopathological findings, immunofluorescence analyses of skeletal muscle and dermal cells derived from the patient showed nuclear shape alterations when compared to control cells. In addition, a significantly reduced nesprin-2 giant protein localisation to the nuclear envelope was observed in patient-derived dermal fibroblasts. Our findings imply that the novel heterozygous SYNE2 mutation results in a monoallelic splicing defect of nesprin-2, thereby leading to a rare cause of myalgia and hyperCKemia

Impact of plain packaging of tobacco products on smoking in adults and children: an elicitation of international experts’ estimates

BACKGROUND: Governments sometimes face important decisions in the absence of direct evidence. In these cases, expert elicitation methods can be used to quantify uncertainty. We report the results of an expert elicitation study regarding the likely impact on smoking rates in adults and children of plain packaging of tobacco products. METHODS: Thirty-three tobacco control experts were recruited from the UK (n = 14), Australasia (n = 12) and North America (n = 7). Experts’ estimates were individually elicited via telephone interviews, and then linearly pooled. Elicited estimates consisted of (1) the most likely, (2) the highest possible, and (3) the lowest possible value for the percentage of (a) adult smokers and (b) children trying smoking, two years after the introduction of plain packaging (all other things being constant) in a target country in the expert’s region of residence. RESULTS: The median estimate for the impact on adult smoking prevalence was a 1 percentage point decline (99% range 2.25 to 0), and for the percentage of children trying smoking was a 3 percentage point decline (99% range 6.1 to 0), the latter estimated impact being larger than the former (P < 0.001, sign test). There were no differences in either estimate by region (I(2): Adults: 0; Children: 0) but there was considerable variability between experts’ estimates within regions (I(2): Adults: 0.91; Children: 0.89). CONCLUSIONS: In the absence of direct evidence for the impact of introducing plain packaging on smoking rates in adults and children, this study shows that tobacco control experts felt the most likely outcomes would be a reduction in smoking prevalence in adults, and a greater reduction in the numbers of children trying smoking, although there was substantial variability in the estimated size of these impacts. No experts judged an increase in smoking as a likely outcome