Severe congenital cutis laxa: Identification of novel homozygous LOX gene variants in two families.

We report three babies from two families with a severe lethal form of congenital cutis laxa. All three had redundant and doughy-textured skin and two siblings from one family had facial dysmorphism. Echocardiograms showed thickened and poorly contractile hearts, arterial dilatation and tortuosity.

Targeted gene panel use in 2249 neuromuscular patients: the Australasian referral center experience.

Objective: To develop, test, and iterate a comprehensive neuromuscular targeted gene panel in a national referral center.

Methods: We designed two iterations of a comprehensive targeted gene panel for neuromuscular disorders. Version 1 included 336 genes, which was increased to 464 genes in Version 2.

Pharmacogenomics in general practice: The time has come.

Background: Patients respond to medications differently because of variations in the genes that determine medication exposure and medication response.

Objective: The aim of this review is to introduce pharmacogenomic testing and explain how to start using pharmacogenomic tests in general practice.

Discussion: Knowledge of the variants in pharmacogenomics is useful when prescribing a variety of medications.

Improved Diagnosis and Care for Rare Diseases through Implementation of Precision Public Health Framework.

Public health relies on technologies to produce and analyse data, as well as effectively develop and implement policies and practices. An example is the public health practice of epidemiology, which relies on computational technology to monitor the health status of populations, identify disadvantaged or at risk population groups and thereby inform health policy and priority setting. Critical to achieving health improvements for the underserved population of people living with rare diseases is early diagnosis and best care.

Genotype and phenotype spectrum of NRAS germline variants.

RASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly conserved RAS-MAPK signalling pathway that lead to dysregulation of cell signal transmission. Germline changes in the genes encoding members of the RAS subfamily of GTPases are rare and associated with variable phenotypes of the RASopathy spectrum, ranging from Costello syndrome (HRAS variants) to Noonan and Cardiofaciocutaneous syndromes (KRAS variants).

Initiating an undiagnosed diseases program in the Western Australian public health system.

Background: New approaches are required to address the needs of complex undiagnosed diseases patients. These approaches include clinical genomic diagnostic pipelines, utilizing intra- and multi-disciplinary platforms, as well as specialty-specific genomic clinics. Both are advancing diagnostic rates.

Detection of copy number variations in melanocytic lesions utilising array based comparative genomic hybridisation.

Distinction between melanocytic naevi and melanoma occasionally poses a diagnostic challenge in ambiguous cases showing overlapping histological features. Melanomas are characterised by the presence of multiple genomic copy number variants (CNVs), while this is not a feature of naevi. We assessed the feasibility and utility of array-based comparative genomic hybridisation (aCGH) to assess CNVs in melanocytic lesions.

The rare and undiagnosed diseases diagnostic service - application of massively parallel sequencing in a state-wide clinical service.

Background: The Rare and Undiagnosed Diseases Diagnostic Service (RUDDS) refers to a genomic diagnostic platform operating within the Western Australian Government clinical services delivered through Genetic Services of Western Australia (GSWA). GSWA has provided a state-wide service for clinical genetic care for 28 years and it serves a population of 2.5 million people across a geographical area of 2.

A germline MTOR mutation in Aboriginal Australian siblings with intellectual disability, dysmorphism, macrocephaly, and small thoraces.

We report on three Aboriginal Australian siblings with a unique phenotype which overlaps with known megalencephaly syndromes and RASopathies, including Costello syndrome. A gain-of-function mutation in MTOR was identified and represents the first reported human condition due to a germline, familial MTOR mutation. We describe the findings in this family to highlight that (i) the path to determination of pathogenicity was confounded by the lack of genomic reference data for Australian Aboriginals and that (ii) the disease biology, functional analyses in this family, and studies on the tuberous sclerosis complex support consideration of an mTOR inhibitor as a therapeutic agent.

Mutations in CYC1, encoding cytochrome c1 subunit of respiratory chain complex III, cause insulin-responsive hyperglycemia.

Many individuals with abnormalities of mitochondrial respiratory chain complex III remain genetically undefined. Here, we report mutations (c.288G>T [p.

Two Australian families with inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia: novel clinical and genetic findings.

We report the first Australian families with inclusion-body myopathy, Paget's disease of the bone and frontotemporal dementia (IBMPFD). The clinical characteristics of the two pedigrees are described including a previously undescribed phenotypic feature of pyramidal tract dysfunction in one family member. A novel mutation in the valosin-containing protein (VCP) gene (p.

An inverse association between preserved fish and prostate cancer: results from a population-based case-control study in Canada.

Epidemiological studies suggest that fish consumption may be a protective factor against the development of prostate cancer. We investigated the association between prostate cancer risk and fresh and preserved fish consumption among participants of a population-based case-control study (1,534 cases, 1,607 controls). Fish intake was measured using a dietary questionnaire that collected both frequency of consumption of a given portion size.

Do aggregates of multiple questions better capture overall fish consumption than summary questions?

Objective: To compare intake estimates, validity and reliability of two summary questions to measure fish consumption with information from a detailed semi-quantitative food-frequency questionnaire (FFQ) on fish consumption.

Design: Population-based, cross-sectional study. Participants completed an FFQ and provided blood samples for erythrocyte membrane eicosapentaenoic acid (EPA) analysis.

Surgical management of lung cancer in Western Australia in 1996 and its outcomes.

Background: All cases of lung cancer diagnosed in Western Australia in 1996 in which surgery was the primary treatment, were reviewed. Reported herein are the characteristics of the patients, the treatment outcomes and a comparison of the management undertaken with that recommended by international guidelines.

Methods: All patients with a new diagnosis of lung cancer in Western Australia in the calendar year of 1996 were identified using two different population-based registration systems: the Western Australian (WA) Cancer Registry and the WA Hospital Morbidity Data System.