Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Reliability of the 50-foot walk test and 30-sec chair stand test in total knee arthroplasty

OBJECTIVE: To investigate the reliability of the 50-Foot Walk Test (50 FWT) and 30-second Chair Stand Test (30 CST) in patients who have undergone total knee arthroplasty (TKA). METHODS: The study was designed as a test-retest research. Thirty-three patients who would undergo bilateral TKA were recruited. The tests 30 CST and 50 FWT were performed twice on the same day with 5-minute intervals, respectively. Between the first and second tests, patients waited for an hour on sitting position in order to prevent fatigue. In addition to these tests, we registered the knee pain experienced by the patients using a 100 mm VAS scale. RESULTS: The 50 FWT and 30 CST showed excellent reliability. ICC for 50 FWT and 30 CST were 0.97 and 0.92, respectively. SRD95 was 1.07 for 50 FWT and 0.96 for 30 CST. CONCLUSIONS: According to results of this study, both 50 FWT and 30 CST have excellent reliability in patients with TKA. These tests are simple, no time consuming and constitute sensitive methods to measure the functional performance in patients with TKA in the clinical settings. Clinicians and researchers may use these tests to quantify even small changes in functional performance for patients with TKA. Level of Evidence III, Diagnostic Study

Management of phenylketonuria in Europe: Survey results from 19 countries

To gain better insight in the most current diagnosis and treatment practices for phenylketonuria (PKU) from a broad group of experts, a European PKU survey was performed. The questionnaire, consisting of 33 questions, was sent to 243 PKU professionals in 165 PKU centers in 23 European countries. The responses were compiled and descriptive analyses were performed. One hundred and one questionnaires were returned by 93/165 centers (56%) from 19/23 European countries (83%). The majority of respondents (77%) managed patients of all age groups and more than 90% of PKU teams included physicians or dieticians/nutritionists. The greatest variability existed especially in the definition of PKU phenotypes, therapeutic blood phenylalanine (Phe) target concentrations, and follow-up practices for PKU patients. The tetrahydrobiopterin (BH4; sapropterin) loading test was performed by 54% of respondents, of which 61% applied a single dose test (20mg/kg over 24h). BH4 was reported as a treatment option by 34%. This survey documents differences in diagnostic and treatment practices for PKU patients in European centers. In particular, recommendations for the treatment decision varied greatly between different European countries. There is an urgent need to pool long-term data in PKU registries in order to generate an evidence-based international guideline