Behavioural and psychological features of PTEN mutations: a systematic review of the literature and meta-analysis of the prevalence of autism spectrum disorder characteristics.

BACKGROUND: Phosphatase and tensin homologue (PTEN) is a cancer suppressor gene. Constitutional mutations affecting this gene are associated with several conditions, collectively termed PTEN hamartoma tumour syndromes (PHTS). In addition to hamartomas, PTEN aberrations have been associated with a range of non-tumoural phenotypes such as macrocephaly, and research indicates possibly increased rates of developmental delay and autism spectrum disorder (ASD) for people with germline mutations affecting PTEN. METHOD: A systematic review of literature reporting behavioural and psychological variables for people with constitutional PTEN mutations/PHTS was conducted using four databases. Following in-depth screening, 25 articles met the inclusion criteria and were used in the review. Fourteen papers reported the proportion of people with PTEN mutations/PTHS meeting criteria for or having characteristics of ASD and were thus used in a pooled prevalence meta-analysis. RESULTS: Meta-analysis using a random effects model estimated pooled prevalence of ASD characteristics at 25% (95% CI 16-33%), although this should be interpreted cautiously due to possible biases in existing literature. Intellectual disability and developmental delay (global, motor and speech and language) were also reported frequently. Emotional difficulties and impaired cognitive functioning in specific domains were noted but assessed/reported less frequently. Methods of assessment of psychological/behavioural factors varied widely (with retrospective examination of medical records common). CONCLUSIONS: Existing research suggests approximately 25% of people with constitutional PTEN mutations may meet criteria for or have characteristics of ASD. Studies have also begun to establish a range of possible cognitive impairments in affected individuals, especially when ASD is also reported. However, further large-scale studies are needed to elucidate psychological/behavioural corollaries of this mutation, and how they may relate to physiological/physical characteristics.

The effect of storage on ammonia, cytokine, and chemokine concentrations in feline whole blood.

OBJECTIVE: To determine if the concentrations of ammonia and inflammatory mediators in feline stored whole blood (SWB) increase with duration of storage. DESIGN: Prospective ex vivo study. SETTING: University Teaching Hospital. ANIMALS: Thirteen cats, recruited from the hospital feline donor pool, deemed healthy based on the predonation donor screening process. INTERVENTIONS: One unit (30 mL) of whole blood was collected from 13 unique blood donor cats, anticoagulated with citrate-phosphate-dextrose, and stored at 4°C. Concentrations of ammonia, interleukin (IL) 6, and IL-10 were measured in 5 units weekly for 4 weeks. Presence of chemokine ligand (CXCL) 8 was measured weekly in 8 other units in the same manner. MEASUREMENTS AND MAIN RESULTS: The ammonia concentration increased nonlinearly with duration of storage, from a median of 48 µmol/L (range 25-74 µmol/L) on day 0 and 417 µmol/L (324-457 µmol/L) on day 28. IL-6 and IL-10 concentrations were below the lower limits of detection of the assay used (IL-6 < 31.2 pg/mL and IL-10 < 125 pg/mL). CXCL-8 was detected in 4 of 8 SWB units at all time points. CONCLUSIONS AND CLINICAL IMPORTANCE: Ammonia concentration increases with storage time in feline SWB. The clinical significance of this finding is yet to be determined. The presence of the proinflammatory chemokine CXCL-8 in feline SWB warrants further research to determine whether it can incite an inflammatory response in the recipient. Further research evaluating the epidemiology of transfusion reactions in cats should evaluate the effect of unit age, and should include the possible impact of the presence of CXCL-8.