Decreased whole-blood global DNA methylation is related to serum hormones in anorexia nervosa adolescents.

OBJECTIVES: The one-carbon metabolism, also known as methionine-homocysteine cycle, governs the dynamics of DNA methylation, epigenetically regulating gene expression, and has been reported altered in anorexia nervosa (AN) adult patients. The aim of this study consisted in assessing whole-blood DNA methylation in adolescent AN patients, assessing its significance in relationship to clinical and hormonal variables. METHODS: Whole-blood global DNA methylation was measured as incorporation of [(3)H]dCTP following HpaII cut in 32 adolescent females affected by restrictive type AN and compared to 13 healthy controls. Homocysteine, vitamin B12 and folate plasma levels were assessed as well as fasting plasma levels of leptin and steroid hormones. Clinical variables, including severity and associate states and traits, were assessed by means of the EDI-3, CDI and STAI-Y scales. RESULTS: We confirm that whole-blood global DNA methylation is modestly albeit significantly reduced in AN adolescents with respect to controls, correlating with plasma leptin and steroid hormone levels. Conversely, clinical traits did not correlate with the outcome variable. CONCLUSIONS: A better definition of the epigenetic dysregulation underlying AN pathology or vulnerability might lead to develop useful markers for diagnosis, prognostic classification and tailored therapeutic interventions in these vulnerable patients since the earliest phases of their disease.

Clinical evaluation and cellular electrophysiology of a recessive CLCN1 patient.

Here we present the case of a 32-year-old female patient with myotonia congenita. She carried two mutations in the CLCN1 gene that encodes the chloride channel ClC-1: p.Phe167Leu, which was previously identified in several families, and p.Val536Leu, which has been previously reported but not yet characterized by electrophysiological investigations. The patient's symptoms included generalized stiffness, myotonia, and muscle cramps mostly localized in the lower limbs. These symptoms started during childhood and worsened over the following years. The symptoms were exacerbated by low outside temperature, rest, stress, and fasting and were improved by mild exercise, suggesting a warm-up phenomenon. The mutation p.Phe167Leu has previously been associated with a slight shift in the overall open probability. Here we further analysed this mutation to extrapolate the voltage-dependence of the fast and slow gates. In our experimental conditions, p.Phe167Leu exclusively affected the slow gate, increasing the minimum open probability and displacing the voltage-dependence toward depolarized potentials. p.Val536Leu showed more severe effects, dramatically influencing the slow gate as well as modifying properties of the fast gate. Co-expression of the mutants in a human cell line to reproduce the compound heterozygous condition of the patient produced channels with altered voltage-dependence of the slow gate but a restored fast gate. The alteration of the slow mechanism was reflected by the relative open probability, reducing the contribution of ClC-1 channels in maintaining the resting membrane potential of skeletal muscles and thus explaining the myotonic phenotype of the patient.