Variable Myopathic Presentation in a Single Family with Novel Skeletal RYR1 Mutation

We describe an autosomal recessive heterogeneous congenital myopathy in a large consanguineous family. The disease is characterized by variable severity, progressive course in 3 of 4 patients, myopathic face without ophthalmoplegia and proximal muscle weakness. Absence of cores was noted in all patients. Genome wide linkage analysis revealed a single locus on chromosome 19q13 with Zmax = 3.86 at θ = 0.0 and homozygosity of the polymorphic markers at this locus in patients. Direct sequencing of the main candidate gene within the candidate region, RYR1, was performed. A novel homozygous A to G nucleotide substitution (p.Y3016C) within exon 60 of the RYR1 gene was found in patients. ARMS PCR was used to screen for the mutation in all available family members and in an additional 150 healthy individuals. This procedure confirmed sequence analysis and did not reveal the A to G mutation (p.Y3016C) in 300 chromosomes from healthy individuals. Functional analysis on EBV immortalized cell lines showed no effect of the mutation on RyR1 pharmacological activation or the content of intracellular Ca²⁺ stores. Western blot analysis demonstrated a significant reduction of the RyR1 protein in the patient’s muscle concomitant with a reduction of the DHPRα1.1 protein. This novel mutation resulting in RyR1 protein decrease causes heterogeneous clinical presentation, including slow progression course and absence of centrally localized cores on muscle biopsy. We suggest that RYR1 related myopathy should be considered in a wide variety of clinical and pathological presentation in childhood myopathies.     

Social Cognition Deficits and Psychopathic Traits in Young People Seeking Mental Health Treatment

Antisocial behaviours and psychopathic traits place an individual at risk for criminality, mental illness, substance dependence, and psychosocial dysfunction. Social cognition deficits appear to be associated with psychopathic traits and are believed to contribute to interpersonal dysfunction. Most research investigating the relationship of these traits with social cognition has been conducted either in children or adult forensic settings. We investigated whether psychopathic traits were associated with social cognition in 91 young people presenting for mental healthcare (aged between 15 and 25 years). Participants completed symptom severity measures, neuropsychological tests, the Reading the Mind in the Eyes Test of social cognition (RMET), and the Antisocial Process Screening Device (APSD) to assess psychopathic personality traits. Correlation analyses showed poorer social cognition was associated with greater psychopathic traits (r = −.36, p = .01). Interestingly, social cognition performance predicted unique variance in concurrent psychopathic personality traits above gender, IQ sustained attention, and working memory performance. These findings suggest that social cognitive impairments are associated with psychopathic tendencies in young people presenting for community mental healthcare. Research is needed to establish the directionality of this relationship and to determine whether social cognition training is an effective treatment amongst young people with psychopathic tendencies.     

Effect of anticoagulants in vitro on the viability of lymphocytes and content of free fatty acids in plasma

Summary These authors attempted to test the effect of anticoagulants on lymphocytes viability by reproducing the procedure used for lymphocyte isolation for various immunologic tests in which blood specimens are allowed to stay at room temperature for 2 h before lymphocytes are isolated. Blood was obtained with three different anticoagulants i.e. heparin, citrate, and CPDA (citrate, phosphate, dextrose, and adenine). Plasma was lyophilized and extracted with ethanol. Dried ethanol extracts were suspended in medium (RPMI 1640+10% fetal bovine serum) and incubated with a lymphocyte cell line (MOLT-4). After 24 h of incubation the viability of cells was examined. The following death rates of the cells were observed: heparin −63±4.6% (mean±SEM), citrate −27±6.7%, and CPDA 6.2±0.6% (P<0.0005). A significant correlation was found between these results and changes in the concentrations of free fatty acids in the extracts. These results emphasize the importance of choosing the right anticoagulant when the viability of lymphocytes is obligatory.