Nationwide, Couple-Based Genetic Carrier Screening.

Background: Genomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition.

Methods: We investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy.

Performance of a cell-free DNA prenatal screening test, choice of prenatal procedure, and chromosome conditions identified during pregnancy after low-risk cell-free DNA screening.

Objectives: To evaluate the performance of cell-free DNA (cfDNA) screening for common fetal aneuploidies, choice of prenatal procedure, and chromosome conditions identified during pregnancy after low-risk cfDNA screening.

Method: A single-center prenatal cfDNA screening test was employed to detect trisomies 21, 18, and 13 (T21, T18, T13) and sex chromosome aneuploidies (SCAs). Test performance, choice of prenatal procedure, and cytogenetic results in pregnancies with low-risk cfDNA screening were reviewed.

Failing the frail: The need to broaden the COVID-19 case definition for geriatric patients.

The older population has a high mortality with COVID-19 and this cohort often presents atypically with infection. This study compares presenting complaints and observations of older patients with COVID-19 against the established case definition to determine whether the case definition should be broadened to better identify SARS-CoV-2 infection in this age group.This retrospective observational study analysed the presenting complaints and observations of people aged 70 years and over who were admitted to a district general hospital with confirmed SARS-CoV-2 infection from March to May 2020.

Genome-wide noninvasive prenatal screening for carriers of balanced reciprocal translocations.

Purpose: Balanced reciprocal translocation carriers are at increased risk of producing gametes with unbalanced forms of the translocation leading to miscarriage, fetal anomalies, and birth defects. We sought to determine if genome-wide cell-free DNA based noninvasive prenatal screening (gw-NIPS) could provide an alternative to prenatal diagnosis for carriers of these chromosomal rearrangements.

Methods: This pilot series comprises a retrospective analysis of gw-NIPS and clinical outcome data from 42 singleton pregnancies where one parent carried a balanced reciprocal translocation.

Correction: Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests.

Zoe McDonald, BSc, was omitted from the list of article coauthors. Her name should have been included as the seventh author, following Clare Elizabeth Hunt. Her affiliation is Victorian Clinical Genetics Services, Parkville, Victoria, Australia.

Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests.

PurposeTo describe our experience of offering simultaneous genetic carrier screening for cystic fibrosis (CF), fragile X syndrome (FXS), and spinal muscular atrophy (SMA).MethodsCarrier screening is offered through general practice, obstetrics, fertility, and genetics settings before or in early pregnancy. Carriers are offered genetic counseling with prenatal/preimplantation genetic diagnosis available to those at increased risk.

Selection of reference gene expression in a schizophrenia brain cohort.

Objective: In order to conduct postmortem human brain research into the neuropatho-logical basis of schizophrenia, it is critical to establish cohorts that are well-characterized and well-matched. The aim of the present study was therefore to determine if specimen characteristics including: diagnosis, age, postmortem interval (PMI), brain acidity (pH), and/or the agonal state of the subject at death related to RNA quality, and to determine the most appropriate reference gene mRNAs.

Methods: A matched cohort was selected of 74 subjects (schizophrenia/schizoaffective disorder, n = 37; controls, n = 37).

The importance of brain banks for molecular neuropathological research: The New South Wales Tissue Resource Centre experience.

New developments in molecular neuropathology have evoked increased demands for postmortem human brain tissue. The New South Wales Tissue Resource Centre (TRC) at The University of Sydney has grown from a small tissue collection into one of the leading international brain banking facilities, which operates with best practice and quality control protocols. The focus of this tissue collection is on schizophrenia and allied disorders, alcohol use disorders and controls.

Cell biology, regulation and inhibition of beta-secretase (BACE-1).

Since the discovery of the beta-secretase responsible for initiating the Alzheimer's amyloid cascade as a novel membrane-bound aspartic proteinase, termed 'beta-site amyloid precursor protein cleaving enzyme', 'aspartyl protease-2' or 'membrane-anchored aspartic proteinase of the pepsin family-2', huge efforts have been devoted to an understanding of its biology and structure in the subsequent decade. This has paid off in many respects, as it has been cloned, its structure solved, novel physiological substrates of the enzyme discovered, and numerous inhibitors of its activity developed in a relatively short space of time. The inhibition of beta-secretase activity in vivo remains one of the most viable strategies for the treatment of Alzheimer's disease, although progress in getting inhibitors to the clinic has been slow, partly as a consequence of its aspartic proteinase character, which poses considerable problems for the production of potent, selective and brain-accessible compounds.