A CASQ1 founder mutation in 3 Italian families with protein aggregate myopathy and hyperCKaemia

Chronic elevation of serum creatine kinase (CK) is a common manifestation of neuromuscular disorders and may precede disease clinical expression, or remain asymptomatic. In 3 Italian families having high CK, mild myopathy, and calsequestrin-positive inclusions in muscle fibers, exome and Sanger sequencing and linkage analysis revealed a founder mutation in the CASQ1 gene. Immunocytochemistry, electron […]

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Continued lessons from the INS gene: an intronic mutation causing diabetes through a novel mechanism

Neonatal diabetes (diagnosed under 6 months of age) is usually caused by a disruption (mutation) in one of over twenty diabetes-related genes. One of the most common causes of neonatal diabetes is mutations in the insulin gene that result in production of a misshaped insulin protein that leads to death of the insulin producing beta […]

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Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4–dihydroxybensoic acid

Coenzyme Q (CoQ10) is an essential mitochondrial electron carrier, redox cofactor and a potent antioxidant in the majority of cellular membranes. A range of metabolic diseases, as well as the ageing process and prolonged statin treatments have been associated with CoQ10 deficiency. Here the first case of a primary CoQ10 defect due to a mutation […]

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Combined Mineralocorticoid and Glucocorticoid deficiency is caused by a novel founder Nicotinamide Nucleotide Transhydrogenase mutation that alters mitochondrial morphology and increases oxidative stress

The novel and ancestral NNT mutation, p.G200S, which was identified in two unrelated consanguineous families, expands the glucocorticoid deficiency phenotype of NNT mutations to include also mineralocorticoid deficiency; and thus present in early life with severe salt loss, low blood pressure and hypoglycemia. We provide the first patient-based evidence that NNT mutations induce oxidative stress […]

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Breakpoint mapping by whole genome sequencing identifies PTH2R gene disruption in a patient with midline craniosynostosis and a de novo balanced chromosomal rearrangement

Craniosynostosis (CRS) is premature closure of cranial sutures, which is caused by either a gene mutation or environmental factors or both. Herein we found a gene mutation causing midline non-syndromic craniosynostosis in a 15-month-old boy. Conventional chromosome study revealed a complex paracentric inversion involving 2q14.3 and 2q34, and multicolor banding refined breakpoints to 2q14 and […]

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Prenatal genomic microarray and sequencing in Canadian medical practice: towards consensus

A brief conference report documents a gathering, sponsored by the University of Toronto’s McLaughlin Centre, of representatives of the Canadian medical genetics community. They were invited to consider issues concerning new genomic technologies in prenatal clinical practice, as a precursor to practice guidelines and recommendations for policy makers. Invited guests provided international experience and insight.   […]

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Streamlining review of research involving humans: Canadian models

Research ethics and data access review are two important milestones that rest on the path from clinical innovation to clinical care. Research ethics review ensures the protection of all research participants, while the data access review facilitates collaboration and data sharing among researchers worldwide. Both reviews, however, can pose significant practical challenges when studies involve […]

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Contribution of the low-frequency, loss-of-function p.R270H mutation in FFAR4 (GPR120) to increased fasting plasma glucose levels

Mice deficient for the lipid sensor Gpr120 develop obesity and both impaired fasting glucose and glucose intolerance under a high-fat diet. In humans, a loss-of-function mutation in /GPR120/ was shown to markedly contribute to obesity. Here, the authors investigate the effect of the same mutation in type 2 diabetes and glucose-related traits. They identified a […]

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