Parenting Intervention and the Prevention of Serious Mental Health Problems in Children

The reduction of coercive or inadequate parenting is essential if the mental health status of Australian children and adolescents is to be improved. Of the available approaches that address parenting practices, behavioural family interventions have the strongest empirical support and are effective in reducing parenting practices that contribute to the development of behavioural and emotional problems in children. However, only a small proportion of parents access such interventions. A comprehensive multilevel, evidence-based parenting and family support strategy needs to be implemented on a wide scale to reduce the prevalence of mental health problems in children and youth. The Triple P – Positive Parenting Program is an example of a population-level strategy that can be used to improve the mental health status of children and their parents

Elucidating the clinical spectrum and molecular basis of HYAL2 deficiency

This is the final version. Available on open access from Elsevier via the DOI in this recordData Availability: The variants listed in this paper have been deposited in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/) with accessions SCV001572828 - SCV001572838.PURPOSE: We previously defined biallelic HYAL2 variants causing a novel disorder in 2 families, involving orofacial clefting, facial dysmorphism, congenital heart disease, and ocular abnormalities, with Hyal2 knockout mice displaying similar phenotypes. In this study, we better define the phenotype and pathologic disease mechanism. METHODS: Clinical and genomic investigations were undertaken alongside molecular studies, including immunoblotting and immunofluorescence analyses of variant/wild-type human HYAL2 expressed in mouse fibroblasts, and in silico modeling of putative pathogenic variants. RESULTS: Ten newly identified individuals with this condition were investigated, and they were associated with 9 novel pathogenic variants. Clinical studies defined genotype-phenotype correlations and confirmed a recognizable craniofacial phenotype in addition to myopia, cleft lip/palate, and congenital cardiac anomalies as the most consistent manifestations of the condition. In silico modeling of missense variants identified likely deleterious effects on protein folding. Consistent with this, functional studies indicated that these variants cause protein instability and a concomitant cell surface absence of HYAL2 protein. CONCLUSION: These studies confirm an association between HYAL2 alterations and syndromic cleft lip/palate, provide experimental evidence for the pathogenicity of missense alleles, enable further insights into the pathomolecular basis of the disease, and delineate the core and variable clinical outcomes of the condition