Reports and Findings

Research

The Human Phenotype Ontology was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas.

Research

Emerging evidence suggests young children are at greater risk of COVID-19 infection than initially predicted. However, a comprehensive understanding of epidemiology of COVID-19 infection in young children under five years, the most at-risk age-group for respiratory infections, remain unclear. We conducted a systematic review and meta-analysis of epidemiological and clinical characteristics of COVID-19 infection in children under five years.

Research

In preparation for the future arrival of a group A Streptococcus (GAS) vaccine, this study estimated the economic and health burdens of GAS diseases in New Zealand. The annual incidence of GAS diseases was based on extrapolation of the average number of primary healthcare episodes managed each year in general practices (2014-2016) and on the average number of hospitalizations occurring each year (2005-2014). Disease incidence was multiplied by the average cost of diagnosing and managing an episode of disease at each level of care to estimate the annual economic burden.

Research

Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide).

Research

Vulvodynia and pudendal neuralgia comprise significant contributors to vulvar-related pain and its impact on daily life. A retrospective clinical audit was conducted at the Women's Health & Research Institute of Australia, Sydney, to determine the pattern of use and the efficacy of the application of topical amitriptyline 0.5% plus oestriol 0.03% in organogel (AOO), to the vulvar vestibule in reducing the impact of pain on daily life.

Research

DYRK1A is a serine/threonine kinase encoded on human chromosome 21 (HSA21) that has been implicated in several pathologies of Down syndrome (DS), including cognitive deficits and Alzheimer's disease. Although children with DS are predisposed to developing leukemia, especially B cell acute lymphoblastic leukemia (B-ALL), the HSA21 genes that contribute to malignancies remain largely undefined. Here, we report that DYRK1A is overexpressed and required for B-ALL. Genetic and pharmacologic inhibition of DYRK1A decreased leukemic cell expansion and suppressed B-ALL development in vitro and in vivo.

Research

Prenatal alcohol and tobacco exposures have been associated with adverse mental health consequences in offspring. The objective of this study was to test the associations between maternal prenatal alcohol and tobacco exposures and depressive symptoms in the offspring, adjusting for a wide range of potential confounders.

Research

Transcriptomic technologies have revolutionized the study of gene expression and RNA biology. Different RNA sequencing methods enable the analyses of diverse species of transcripts, including their abundance, processing, stability, and other specific features. Mitochondrial transcriptomics has benefited from these technologies that have revealed the surprising complexity of its RNAs. Here we describe a method based upon cyclization of mitochondrial RNAs and next generation sequencing to analyze the steady-state levels and sizes of mitochondrial RNAs, their degradation products, as well as their processing intermediates by capturing both 5' and 3' ends of transcripts.

Research

Characterized by early-onset seizures, global developmental delay and severe motor deficits, CDKL5 deficiency disorder is caused by pathogenic variants in the cyclin-dependent kinase-like 5 gene. Previous efforts to investigate genotype-phenotype relationships have been limited due to small numbers of recurrent mutations and small cohort sizes. Using data from the International CDKL5 Disorder Database we examined genotype-phenotype relationships for 13 recurrent CDKL5 variants and the previously analyzed historic variant groupings. We have applied the CDKL5 Developmental Score (CDS) and an adapted version of the CDKL5 Clinical Severity Assessment (CCSA), to grade the severity of phenotype and developmental outcomes for 285 individuals with CDKL5 variants.

Research

The design of a videolaryngoscope blade may affect its efficacy. We classified videolaryngoscope blades as standard and non-standard shapes to compare their efficacy performing tracheal intubation in children enrolled in the Paediatric Difficult Intubation Registry.