Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.

PurposeGenetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use.MethodsWe prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing.ResultsWGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24%; P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A.ConclusionWGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort.

Laps or lengths? The effects of different exercise programs on asthma control in children.

INTRODUCTION: Exercise training has been shown in numerous studies to improve lung function and asthma control in children with asthma. Swimming has been shown to be of benefit in children with asthma, but which form of exercise is better for asthmatics has not been determined to date. The aim of this study was to examine if swimming improved lung function and asthma symptoms in asthmatic children when compared with different forms of exercise and a control group. METHODS: Subjects with asthma were randomly assigned to either one of three different exercise training groups (swimming, football, and basketball) or a control group. Spirometry was performed before and after and the subjects were asked to keep asthma diaries and perform daily peak flow measurements. RESULTS: 41 children and adolescents between the ages of 9 and 16 participated in the study. After completing the training, children across all three exercise programs had significantly higher forced vital capacity (FVC) percentage values when compared to the control group. The swimming group demonstrated a significant increase in the percentage peak expiratory flow (PEF) following the exercise program when compared with the control group (78.3 ± 9.3 versus 89.0 ± 14.9, p = 0.04). All children on exercise training programs reported an improvement in their asthma symptoms via asthma diaries. CONCLUSION: This study suggests that a swimming training program is more beneficial in terms of peak flow measurements when compared with other exercise training programs.

Kids in transition: the rehab experience.

Holland Bloorview Kids Rehabilitation Hospital (formerly Bloorview Kids Rehab) is Canada's largest teaching hospital for pediatric rehabilitation and the only in-patient pediatric rehabilitation centre in Ontario. SickKids is a quaternary-level academic health sciences centre. The acute care neuroscience and trauma patient population at SickKids represents the largest volume of transitioning clients between the two organizations. For years, the number of medically unnecessary days associated with patients awaiting transfer from SickKids to Holland Bloorview for off-site rehabilitation was consistently driven by inefficient processes, multiple handovers, duplicitous efforts, fragmented communication and a lack of timely or complete referral information. Recognizing this situation as a threat to access, as well as a significant risk to patient health outcomes, SickKids and Holland Bloorview embarked on an exciting partnership (Kids in Transition: The Rehab Experience) as part of a larger Ministry of Health and Long-Term Care-funded initiative, the Flo Collaborative.

Thiopurine S-methyltransferase testing for averting drug toxicity in patients receiving thiopurines: a systematic review.

AIM: Thiopurine S-methyltransferase (TPMT) testing is used in patients receiving thiopurines to identify enzyme deficiencies and risk for adverse drug reactions. It is uncertain whether genotyping is superior to phenotyping. The objectives were to conduct a systematic review of TPMT-test performance studies. MATERIALS & METHODS: Electronic and grey literature sources were searched for studies reporting test performance compared with a reference standard. Sixty-six eligible studies were appraised for quality. RESULTS: Thirty phenotype-genotype and six phenotype-phenotype comparisons were of high quality. The calculated sensitivity and specificity for genotyping to identify a homozygous mutation ranged from 0.0-100.0% and from 97.8-100.0%, respectively. CONCLUSION: Clinical decision-makers require high-quality evidence of clinical validity and clinical utility of TPMT genotyping to ensure appropriate use in patients.