Families' healthcare experiences for children with inherited metabolic diseases: protocol for a mixed methods cohort study.

Introduction: Children with inherited metabolic diseases (IMDs) often have complex and intensive healthcare needs and their families face challenges in receiving high-quality, family centred health services. Improvement in care requires complex interventions involving multiple components and stakeholders, customised to specific care contexts. This study aims to comprehensively understand the healthcare experiences of children with IMDs and their families across Canada.

SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females.

Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms.

Parkinsonism in Patients with Neuronopathic (Type 3) Gaucher Disease: A Case Series.

Background: The link between Parkinson's disease (PD), the second most common neurodegenerative disorder, and nonneuronopathic Gaucher disease (GD) is well established. Currently, PD is primarily associated with nonneuronopathic GD; however, with currently available treatments, patients with chronic neuronopathic GD, who historically had a shortened life span, are now living well into their 50s and beyond.

Cases: We highlight 4 patients with chronic neuronopathic GD with parkinsonian features, describing their GD genotype and phenotype as well as the presentation and progression of their parkinsonism.

A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1.

Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways. Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development.

Bridging the gap in genetics: a progressive model for primary to specialist care.

Background: The rapid expansion of genetic knowledge, and the implications for healthcare has resulted in an increased role for Primary Care Providers (PCPs) to incorporate genetics into their daily practice. The objective of this study was to explore the self-identified needs, including educational needs, of both urban and rural Primary Care Providers (PCPs) in order to provide genetic care to their patients.

Methods: Using a qualitative grounded theory approach, ten key informant interviews, and one urban and two rural PCP focus groups (FGs) (n = 19) were conducted.

Student Reflections on the Queen's Accelerated Route to Medical School Programme.

Context: Since its inception more than 150 years ago, the School of Medicine at Queen's University has aspired 'to advance the tradition of preparing excellent physicians and leaders in health care by embracing a spirit of inquiry and innovation in education and research'. As part of this continuing commitment, Queen's School of Medicine developed the Queen's University Accelerated Route to Medical School (QuARMS). As Canada's only 2-year accelerated-entry premedical programme, QuARMS was designed to reduce training time, the associated expense of medical training, and to encourage a collaborative premedical experience.

Primary care providers' lived experiences of genetics in practice.

To effectively translate genetic advances into practice, engagement of primary care providers (PCPs) is essential. Using a qualitative, phenomenological methodology, we analyzed key informant interviews and focus groups designed to explore perspectives of urban and rural PCPs. PCPs endorsed a responsibility to integrate genetics into their practices and expected advances in genetic medicine to expand.

Computational Prediction of Position Effects of Apparently Balanced Human Chromosomal Rearrangements.

Interpretation of variants of uncertain significance, especially chromosomal rearrangements in non-coding regions of the human genome, remains one of the biggest challenges in modern molecular diagnosis. To improve our understanding and interpretation of such variants, we used high-resolution three-dimensional chromosomal structural data and transcriptional regulatory information to predict position effects and their association with pathogenic phenotypes in 17 subjects with apparently balanced chromosomal abnormalities. We found that the rearrangements predict disruption of long-range chromatin interactions between several enhancers and genes whose annotated clinical features are strongly associated with the subjects' phenotypes.

Mutations in the Chromatin Regulator Gene BRPF1 Cause Syndromic Intellectual Disability and Deficient Histone Acetylation.

Identification of over 500 epigenetic regulators in humans raises an interesting question regarding how chromatin dysregulation contributes to different diseases. Bromodomain and PHD finger-containing protein 1 (BRPF1) is a multivalent chromatin regulator possessing three histone-binding domains, one non-specific DNA-binding module, and several motifs for interacting with and activating three lysine acetyltransferases. Genetic analyses of fish brpf1 and mouse Brpf1 have uncovered an important role in skeletal, hematopoietic, and brain development, but it remains unclear how BRPF1 is linked to human development and disease.

Parents' Understanding of Genetics and Heritability.

Parents have the opportunity to educate their children to facilitate behaviours and lifestyle habits that may prevent or delay genetic disease, or mitigate predispositions within the family. We sought to determine parents' understanding of genetic knowledge and heritability. Using a quantitative survey methodology 108 volunteer participants were surveyed from a convenience sample of all parents/caregivers within the waiting room of a general children's outpatient clinic.

Melanocortin-4 Receptor Deficiency Phenotype with an Interstitial 18q Deletion: A Case Report of Severe Childhood Obesity and Tall Stature.

Childhood obesity is a growing health concern, associated with significant physical and psychological morbidity. Childhood obesity is known to have a strong genetic component, with mutations in the () gene being the most common monogenetic cause of obesity. Over 166 different mutations have been identified in persons with hyperphagia, severe childhood obesity, and increased linear growth.

Congenital myopathy with cap-like structures and nemaline rods: case report and literature review.

Background: Cap myopathy is a rare congenital myopathy characterized by cap structures located at the periphery of the muscle fiber. Cap structures consist of disarranged thin filaments with enlarged Z discs. The clinical presentation and natural history of cap myopathy is variable and overlaps with other congenital myopathies.

X-linked deafness-2 (DFNX2) phenotype associated with a paracentric inversion upstream of POU3F4.

Purpose: The authors report on a 7-year-old male, designated FR, who has severe sensorineural hearing loss. Features include a round face, hypertelorism, epicanthal folds, and flat nasal root. Although there were early developmental concerns regarding FR, all but his speech delay resolved when he was placed in an educational program that accommodated his hearing loss.

Gaucher disease associated with parkinsonism: four further case reports.

Type 1 Gaucher disease is considered the non-neuronopathic form of this autosomal recessively inherited lysosomal storage disease. We report the simultaneous occurrence of Gaucher disease with parkinsonian in four adult patients. The patients had a relatively early onset of parkinsonian manifestations, and their disease was rapidly progressive and refractory to therapy.