A novel HRAS c.466C>T p.(Phe156Leu) variant in two patients with attenuated features of Costello syndrome.

Costello syndrome (CS) is caused by heterozygous HRAS germline mutations. Most patients share the HRAS variant p.Gly12Ser that is associated with a typical, homogeneous phenotype.

Genomic testing for children with interstitial and diffuse lung disease (chILD): parent satisfaction, understanding and health-related quality of life.

Objective: Research is needed to determine best practice for genomic testing in the context of child interstitial or diffuse lung disease (chILD). We explored parent's and child's health-related quality of life (HRQoL), parents' perceived understanding of a genomic testing study, satisfaction with information and the study and decisional regret to undertake genomic testing.

Methods: Parents of children with diagnosed or suspected chILD who were enrolled in a genomic sequencing study were invited to complete questionnaires pretesting (T1) and after receiving the result (T2).

Standardized practices for RNA diagnostics using clinically accessible specimens reclassifies 75% of putative splicing variants.

Purpose: Genetic variants causing aberrant premessenger RNA splicing are increasingly being recognized as causal variants in genetic disorders. In this study, we devise standardized practices for polymerase chain reaction (PCR)-based RNA diagnostics using clinically accessible specimens (blood, fibroblasts, urothelia, biopsy).

Methods: A total of 74 families with diverse monogenic conditions (31% prenatal-congenital onset, 47% early childhood, and 22% teenage-adult onset) were triaged into PCR-based RNA testing, with comparative RNA sequencing for 19 cases.

Review of the radiation exposure during screening of surgically implanted central venous access devices.

Purpose: Ionizing radiation is used for the insertion of surgically implanted venous access devices (SIVADs) with children at the highest risk of cumulative radiation effects from these procedures. This study examines the radiation dose in a pediatric population during intraoperative radiological screening.

Methods: A retrospective study looked at all pediatric patients in a tertiary hospital between January 2008 and January 2014 who had a surgically implanted venous access device inserted using intraoperative fluoroscopy.

Regional differences in susceptibiity of bronchial epithelium to mesenchymal transition and inhibition by the macrolide antibiotic azithromycin.

Objective: Dysregulated repair following epithelial injury is a key forerunner of disease in many organs, and the acquisition of a mesenchymal phenotype by the injured epithelial cells (epithelial to mesenchymal transition, EMT) may serve as a source of fibrosis. The macrolide antibiotic azithromycin and the DNA synthesis inhibitor mycophenolate are in clinical use but their mechanism of action remains unknown in post-transplant bronchiolitis obliterans syndrome (BOS). Here we determined if regional variation in the EMT response to TGFβ1 underlies the bronchiolocentric fibrosis leading to BOS and whether EMT could be inhibited by azithromycin or mycophenolate.