Some individuals with a particular disease-causing mutation or genotype fail to express most if not all features of the disease in question, a phenomenon that is known as ‘reduced (or incomplete) penetrance’. Reduced penetrance is not uncommon; indeed, there are many known examples of ‘disease-causing mutations’ that fail to cause disease in at least a proportion of the individuals who carry them. Reduced penetrance may therefore explain not only why genetic diseases are occasionally transmitted through unaffected parents, but also why healthy individuals can harbour quite large numbers of potentially disadvantageous variants in their genomes without suffering any obvious ill effects. Reduced penetrance can be a function of the specific mutation(s) involved or of allele dosage. It may also result from differential allelic expression, copy number variation or the modulating influence of additional genetic variants in cis or in trans. The penetrance of some pathogenic genotypes is known to be age- and/or sex-dependent. Variable penetrance may also reflect the action of unlinked modifier genes, epigenetic changes or environmental factors. At least in some cases, complete penetrance appears to require the presence of one or more genetic variants at other loci. In this review, we summarize the evidence for reduced penetrance being a widespread phenomenon in human genetics and explore some of the molecular mechanisms that may help to explain this enigmatic characteristic of human inherited disease.

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Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease

This review summarizes the existing knowledge regarding the effects of physical exercise in patients suffering from multiple sclerosis (MS). Furthermore, recommendations are given regarding exercise prescription for MS patients and for future study directions. Previously, MS patients were advised not to participate in physical exercise. During recent years, it has been increasingly acknowledged that exercise benefits MS patients. The requirement for exercise in MS patients is emphasized by their physiological profile, which probably reflects both the effects of the disease per se and the reversible effects of an inactive lifestyle. To date the effects of exercise have only been studied in moderately impaired MS patients with an EDSS score of less than 7. Evidence exists for recommending participation in endurance training at low to moderate intensity, as the existing literature demonstrates that MS patients can both tolerate and benefit from this training modality. Also, resistance training of moderate intensity seems to be well tolerated and to have beneficial effects on MS patients, but the methodological quality of the existing evidence is in general low and the number of studies is limited. Only two studies have evaluated the effects of combined resistance- and endurance training, making solid conclusions regarding this training modality impossible.

Multiple sclerosis and physical exercise: recommendations for the application of resistance-, endurance- and combined training.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/j.molonc.2010.04.011

Genetic susceptibility to breast cancer

Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established. Here, we present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE. The proposed mechanism explains 4 major characteristics associated with autism: the low concentrations of serotonin in the brain and its elevated concentrations in tissues outside the blood-brain barrier; the low concentrations of the vitamin D hormone precursor 25-hydroxyvitamin D [25(OH)D3]; the high male prevalence of autism; and the presence of maternal antibodies against fetal brain tissue. Two peptide hormones, oxytocin and vasopressin, are also associated with autism and genes encoding the oxytocin-neurophysin I preproprotein, the oxytocin receptor, and the arginine vasopressin receptor contain VDREs for activation. Supplementation with vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder.

/pdf/vitamin-d-hormone-regulates-serotonin-synthesis-part-1-4lbyeenif6.pdf

Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism

https://archive-ouverte.unige.ch/unige:111231/ATTACHMENT01

ESPEN guideline clinical nutrition in neurology

Objectives: (1) Evaluate the impact of the patient charateristics of disability, gender and employment status on health-related quality of life (HRQOL) in multiple sclerosis (MS) and (2) Characterize the functional relationship between HRQOL and disability overall, and by gender and employment status. Methods: We assessed the HRQOL of 215 MS outpatients in our clinic using the MSQOL-54 and Fatigue Severity Scale (FSS), and that of 172 healthy controls, using the SF-36 (a subset of MSQOL-54). We compared QOL between MS subgroups defined by disability, gender and employment, and computed the linear and non-linear relationships between disability level measured by the Expanded Disability Status Scale (EDSS) and MSQOL-54 dimensions. Results: QOL of MS patients measured by SF-36 is lower than controls, varying by QOL dimension with the greatest difference emerging for physical aspects of the disease. The relationship of physical disability, measured by EDSS, and all 14 MSQOL-54 dimensions and FSS is negative; for 12 of the 14 dimensions and FSS it is also non-linear. Non-linearity is most pronounced among women, who show a weak EDSS/QOL relatioship at higher levels of physical disability, suggesting women better able to “psychologically buffer” the debilitating aspects of MS. While employed have higher QOL than unemployed, the former are more affected by physical disability. Conclusions: Multiple attributes, including disability, gender and employment status, affect QOL. QOL’s relationship with disability is complex, displaying non-linearity and interacting with patient characteristics. This has implication for QOL research methodology and provides insight into factors affecting patients’ perceptions of well-being.

Health-related quality of life in multiple sclerosis: The impact of disability, gender and employment status.

Background
Flu-like symptoms (FLS) are common side effects of interferon beta (IFN-β) treatment in patients with Multiple Sclerosis (PwMS) and are associated with post-injection cytokine surge. We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines’ levels.

/pdf/vitamin-d-supplementation-for-patients-with-multiple-484dspca23.pdf

Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties

Online health information and services for patients were suggested to improve symptom management and treatment adherence, thereby contributing to healthcare optimization. This paper aimed to characterize multiple sclerosis (MS) patients Internet usage. Information regarding browsing habits, Internet reliability, and the medical team's attitude to information collected online was obtained by questionnaires from MS patients. Data was compared between nonbrowsers, browsers on MS topics, and browsers on non-MS topics only. From the 96 patients recruited, 61 (63.5%) performed MS-related searches. The most viewed topics were “understanding the disease” and “treatments”. Patients reported that the information helped coping with MS and assured them of the appropriateness of their therapy. Shorter disease duration was correlated with higher Internet activity. Disabled patients were more interested in online interaction with specialists and support groups. This paper suggests that MS patients benefit from online information, and it emphasizes the importance of resources tailored to patients needs.

/pdf/internet-usage-by-patients-with-multiple-sclerosis-kxv5c7g5i7.pdf

Internet Usage by Patients with Multiple Sclerosis: Implications to Participatory Medicine and Personalized Healthcare

Objective: To assess the relation between stress caused by the perils of rocket attack on civilian centers in northern Israel during the 2006 war between Hezbollah and Israel and multiple sclerosis (MS) exacerbations. Methods: Participants were 156 patients with relapsing-remitting MS. We compared the number of relapses during and after the war with similar time periods at the preceding year. Exposure to war events and resulting subjective stress were evaluated by means of structured interviews using questionnaires previously validated. Results: During the 33 days of the war, there were 18 relapses among our patients, compared with 1 to 6 relapses in similar time periods over the 12 months before the war ( p 0.001– 0.02). There was no increase in relapse rate during the 3 months that followed the war ( p 0.58). The percentage of patients reporting the experience of intense subjective stress during the hostilities was significantly greater among patients with wartime relapse compared with the rest of the patients (44 vs 20%). The proportion of patients reporting high levels of distress associated with exposure to rocket attacks, displacement from home, and perceived life threat was greater in relapsing patients compared with those in remission (67 vs 42%, p 0.05; 33 vs 11%, p 0.02; and 33 vs 15%, p 0.08, respectively). Interpretation: Our data suggest that civilian exposure to war stress is associated with increased risk for MS relapse. These findings provide insight to stress-related risk factors associated with relapses of MS.

/pdf/impact-of-exposure-to-war-stress-on-exacerbations-of-28zymwnzbk.pdf

Impact of exposure to war stress on exacerbations of multiple sclerosis.

Objective: Measuring health-related quality of life (HRQoL) enables attainment of a comprehensive picture of chronic patients’ conditions. The aim was to gain insight into HRQoL as viewed by Israeli multiple sclerosis (MS) patients, with an eye to its cross-cultural applicability, using psychometric analysis and a regression-based procedure. Methods: The reliability and validity of the MSQoL-54 was assessed in 215 Israeli MS patients. Subsequently, a novel method in QoL research for assessing the relative importance to patients of different aspects of the construct, comparing these between males and females, was applied. Using factor analysis, the degree to which the MSQoL-54 dimensions are applicable in our population and the existence of a separate dimension of Fatigue were tested. Finally, structural equation modelling (SEM) was used to examine relationships between QoL dimensions. Results: The MSQoL-54 showed reliabilities and validities comparable to those found in other populations. Females attach i...

Sara Dishon

Papers

Health-related quality of life in multiple sclerosis: The impact of disability, gender and employment status.

Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties

Internet Usage by Patients with Multiple Sclerosis: Implications to Participatory Medicine and Personalized Healthcare

Impact of exposure to war stress on exacerbations of multiple sclerosis.

Health-related quality of life in multiple sclerosis: psychometric analysis of inventories: