Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation.

Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing.

Recommendations by the ClinGen Rett/Angelman-like expert panel for gene-specific variant interpretation methods.

The genes MECP2, CDKL5, FOXG1, UBE3A, SLC9A6, and TCF4 present unique challenges for current ACMG/AMP variant interpretation guidelines. To address those challenges, the Rett and Angelman-like Disorders Variant Curation Expert Panel (Rett/AS VCEP) drafted gene-specific modifications. A pilot study was conducted to test the clarity and accuracy of using the customized variant interpretation criteria.

Australia and New Zealand renal gene panel testing in routine clinical practice of 542 families.

Genetic testing in nephrology clinical practice has moved rapidly from a rare specialized test to routine practice both in pediatric and adult nephrology. However, clear information pertaining to the likely outcome of testing is still missing. Here we describe the experience of the accredited Australia and New Zealand Renal Gene Panels clinical service, reporting on sequencing for 552 individuals from 542 families with suspected kidney disease in Australia and New Zealand.

Genome-wide transcriptomic and proteomic studies of Rett syndrome mouse models identify common signaling pathways and cellular functions as potential therapeutic targets.

The discovery that Rett syndrome is caused by mutations in the MECP2 gene has provided a major breakthrough in our understanding of the disorder. However, despite this, there is still limited understanding of the underlying pathophysiology of the disorder hampering the development of curative treatments. Over the years, a number of animal models have been developed contributing to our knowledge of the role of MECP2 in development and improving our understanding of how subtle expression levels affect brain morphology and function.

RettBASE: Rett syndrome database update.

Rett syndrome (RTT) is an X-linked progressive neurodevelopmental disorder that primarily affects females. Mutations in the MECP2 gene have been attributed as the major genetic cause of RTT. Recently, mutations in CDKL5 and FOXG1 genes have also been suggested to give rise to RTT, although subsequent more extensive studies suggest that diseases resulting from mutations in these two genes should be considered as distinct clinical entities.

Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder.

Objective: To investigate seizure outcomes and their relationships to genotype and functional abilities in individuals with the cyclin-dependent kinase-like-5 (CDKL5) disorder.

Methods: Using the International CDKL5 Disorder Database, we identified 172 cases with a pathogenic CDKL5 mutation. We categorized individual mutations into 4 groups based on predicted structural and functional consequences.

The Genome of a Southern Hemisphere Seagrass Species (Zostera muelleri).

Seagrasses are marine angiosperms that evolved from land plants but returned to the sea around 140 million years ago during the early evolution of monocotyledonous plants. They successfully adapted to abiotic stresses associated with growth in the marine environment, and today, seagrasses are distributed in coastal waters worldwide. Seagrass meadows are an important oceanic carbon sink and provide food and breeding grounds for diverse marine species.