Carries the two mutations on separate alleles and that during spermatogenesis a cross-over did occur leaving the two mutations on one allele inherited by the patient, and another normal inherited by the other children. Structurally, the two mutations leading to amino acids substitution at both the N and C terminal of the protein were predicted to be pathogenic, and in our in vitro analysis we did show that the double mutation affects both the transcriptional activity and the localization of the protein. At the subcellular localization level, most of the NFATC1 double mutant proteins failed to translocate to the nucleus when co-expressed with constitutively active calcineurin. Although the mutation is not within the calcineurin docking site, we do suggest that the distorted structure of the protein doesn’t allow proper dephosphorylation of its N-terminal domain. This is supported by the results obtained in gel shift experiments whereby the DNA binding activity was significantly reduced by 30–40% although the same amount of overepressed proteins was used for both wild type and mutant NFATC1. On the other hand, the structure function analysis done on the most expressed isoform, Isoform A, does also mask a possible effect the mutation I701L could have on the sumolation process on isoform C which occurs on K702. The severely malnourished and disturbed biochemical status of patients with MK-1775 Anorexia Nervosa is a fundamental clinical and somatic aspect of the disorder. Clinical consensus agrees that psychological disturbances in AN patients, such as depression and anxiety symptoms, are partly complications of malnutrition. Several hypotheses and mechanisms have been proposed to explain this impact; studies have shown implications of the serotonergic system in mood and depression symptoms; starved AN patients might be having low tryptophan intake, the precursor of serotonin, which is affecting their mood. Another hypothesis is the effect of low leptin levels in AN due to low adiposity, shown to have functional role in depression anxiety and cognitive behaviour. Another approach is related to vitamins and minerals deficiencies and their replenishment. In fact, almost all vitamins have key roles in the brain functions and the nervous system. In the same time, vitamins deficiencies are very common and chronic in AN patients. Other various theories have arisen concerning macronutrients intake, specifically carbohydrates and low carbohydrates diets affecting the mood and creating depression-like symptoms. AN patients, tend to have very low carbohydrates diets and low fat diets, which might affect negatively their mood on the long term. Evidence-based data on this relationship in AN is still very scarce. We recently reviewed all the studies that investigated this relationship in AN. Some simply observed an improvement in psychological condition during nutrition rehabilitation, while the others reported inconsistent findings with no correlation between malnutrition and psychological symptoms. Three limitations were found across most of the studies reviewed. Firstly, they used only body weight or body mass index for the nutritional assessment. Secondly, they did not always report on medication, or if they did, it was not included in the analysis of results. Lastly, they did not include confounding factors such as duration of illness, AN subtype or age. In fact the duration of the illness itself can lead to depressive symptoms, as in any chronic disease. Nutritional assessment cannot be based solely on BMI or body weight. The limitations of these methods of nutritional assessment have been outlined in our recent review. Although BMI is a widely accepted screening tool for obesity, its specificity and sensitivity in undernutrition are unknown.