Myopia incidence is reaching epidemic proportions in some communities, especially in East Asia regions. Meta-association analysis was used to determine if the vasoactive intestinal peptide receptor 2 (VIPR2) associated with myopia a human Chinese cohort, and then conform it using Vipr2-KO mice. Presence of variant in the VIPR2 gene and loss of VIPR2 function in […]
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Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region
Over 2,400 years ago, Hippocrates noticed that eye misalignment, or strabismus, tended to cluster in families. This observation represents an early recognition of what we now recognize as genetic causes. However, genetic causes of isolated strabismus, which occur in the absence of other symptoms, remain elusive. In a large family, we identify a piece […]
Combining evidence for and against pathogenicity for variants in cancer susceptibility genes: CanVIG-UK consensus recommendations
Standardization of practice in classification of variants in cancer susceptibility genes has improved substantially since UK adoption of the 2015 American College of Medical Genetics (ACMG) framework. However, considerable inconsistency between laboratories persists, largely around how evidence items are weighted and combined. We present consensus recommendations from Cancer Variant Interpretation Group UK (CanVIG-UK), our national […]
MELAS-associated m.5541C>T mutation caused instability of mitochondrial tRNATrp and remarkable mitochondrial dysfunction
We found a pathogenic m.5541C>T mutation in the mitochondrial tRNATrp gene in a large MELAS family. This mutation firstly affected the maturation and stability of mitochondrial tRNATrp and impaired mitochondrial respiratory chain complex activities, followed by remarkable mitochondrial dysfunction. Surprisingly, we identified that the supplementation of taurine alone remarkably ameliorated the instability and the translation […]
Canadian College of Medical Geneticists (CCMG) points to consider: resuming genetic services in a pandemic—a summary
The COVID-19 pandemic has disrupted the provision of genetic care in Canada. As genetic services are asked to gradually resume, a roadmap is needed to ensure that clinical care decisions for at-risk patients are transparent and equitable, that postponed care is resumed and that patients with or waiting for a genetic diagnosis are not disproportionately […]
Inhibition of G-protein signaling in cardiac dysfunction of Intellectual Developmental Disorder with Cardiac Arrhythmia (IDDCA) syndrome
IDDCA (MIM #617173) is an ultra-rare autosomal recessive disorder caused by mutations in GNB5 gene. Genotype-phenotype correlation shows that homozygous or compound heterozygous missense variants are associated with an attenuated phenotype with mild intellectual disability (ID) and sinus node dysfunction, while homozygous null alleles cause severe ID with absent speech, epileptic encephalopathy, hypotonia and sinus […]
Prenatal features in Beckwith-Wiedemann syndrome and indications for prenatal testing
Beckwith–Wiedemann syndrome (BWSp) is a medical condition characterized by overgrowth, birth defects and increased risk of cancer during childhood. It affects 1 in 10,000 newborns worldwide. During pregnancy the presentation may be non-specific and the diagnosis is usually suspected after birth, complicating the management of pregnancy, delivery and the neonatal period. We studied the prenatal […]
Dilated cardiomyopathy caused by truncating titin variants: long-term outcomes, arrhythmias, response to treatment and sex differences
Truncations of titin (TTNtv) is the most common genetic cause of dilated cardiomyopathy (DCM). In this study, we investigated the long-term natural history of DCM caused by TTNtv. In our study, we report longer follow-up times (median of 8 years) than previous studies and found that most patients were diagnosed with severe heart failure in […]
Targeted deep sequencing of DNA from multiple tissue types improves the diagnostic rate and reveals a highly diverse phenotype of mosaic neurofibromatosis type 2
Although 60% of de novo Neurofibromatosis type 2 (NF2) patients are presumed to have mosaic NF2, the actual diagnostic rate of this condition remains low at around 20% because of the existing difficulties in detecting NF2 variants with low variant allele frequency. We have improved the diagnostic rate of mosaic NF2 by targeted deep sequencing […]
Stay at home: Implementation and impact of virtualizing cancer genetic services during COVID-19
Stay at home: Implementation and impact of virtualizing cancer genetic services during COVID-19 discusses the adaptations taken by a mainstay Canadian cancer genetics centre to adapt to physical distancing requirements and continue providing services during the global COVID-19 pandemic. These adaptations included virtualization of patients and staff through implementing electronic patient records, moving all appointments […]