Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuromuscular disorder affecting more than 1 in 2500 people. Molecular defects that cause CMT are complex and involve large number of genes. This is the first Canadian study describing results of clinical genetic testing of nearly 3000 patients. This is also the largest patient cohort published to […]
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Understanding polygenic models, their development and the potential application of polygenic scores in healthcare (Contributed by Dr. Chantal Babb de Villiers)
The use of genomic information in the form of polygenic scores as a predictive biomarker for common diseases has been an area of increasing interest. Methods applied in this field have evolved rapidly recently, with several methods proposed in generating these scores. An understanding of these methodological aspects is useful for considerations around implementation in […]
Uptake of pre-symptomatic testing for BRCA1 and BRCA2 is age, gender, offspring and time dependent (Contributed by Dr. Claire Forde)
Predictive BRCA1/2 testing, offered to healthy individuals after a BRCA1/2 gene change is identified in an affected family member, allows relatives to undergo cancer risk assessment and consider early cancer detection and risk-reduction strategies. This study is the largest assessment of BRCA1/2 predictive testing uptake in close relatives, encompassing 5669 individuals from 1564 families, for […]
Novel genetic characterisation and phenotype correlation in von Hippel-Lindau (VHL) disease based on the Elongin C binding site: a large retrospective study (Contributed by Dr. Haibiao Xie)
The highlight of this study is that, based on the current largest VHL patient database and blood sample bank in China, the impact of different gene mutation types of VHL disease on tumor risk and prognosis was analyzed for the first time from the perspective of the Elongin C binding site mutation (EM). This study […]
Identifying novel oncogenic RET mutations and characterising their sensitivity to RET-specific inhibitors (Contributed by Dr. Yu Yao)
Mutations in a cancer-related gene called RET were mainly found in certain cancers such as thyroid cancer. By analyzing large-scale DNA sequencing data from 37,056 cancer patients, we discovered RET mutations in multiple other cancers, mostly at low frequencies. In addition, we identified several novel RET mutations that can drive tumor formation, and some newly […]
Identification of known and unknown genes associated with mitral valve prolapse using an exome slice methodology (Contributed by Dr. Aniek van Wijngaarden)
This study presents the first, large-scale exome-based analysis in patients with (familial) mitral valve prolapse (MVP). We confirmed the occurrence of variant(s) in previously reported genes and proposed possible novel candidate genes for MVP, mostly cardiomyopathy genes. Our findings support familial screening in MVP patients in order to eventually identify affected relatives at an early […]
Medical and neurobehavioural phenotypes in carriers of X-linked ichthyosis-associated genetic deletions in the UK Biobank (Contributed by Dr. William Davies)
X-linked ichthyosis (XLI) is a skin disorder caused by a genetic deletion carried by approximately 7 million individuals worldwide. Brcic and colleagues use the power of the UK Biobank (comprising ~0.5 million individuals recruited from the UK general population) to show that carriers of XLI-associated deletions are at increased risk of mood symptoms and mild […]
A homozygous UBA5 pathogenic variant causes a fatal congenital neuropathy (Contributed by Dr. Macarena Cabrera)
A large consanguineous family was studied after 5 babies died in infancy. The affected individuals present with weakness and poor muscle tone from birth, which progressed to respiratory failure causing death at an early age. Examination and ancillary tests showed a severe peripheral neuropathy, but not central nervous system abnormalities were observed. A homozygous novel […]
Cancer Variant Interpretation Group UK (CanVIG-UK): an exemplar national subspecialty multidisciplinary network (Contributed by Dr. Alice Garrett)
Accurate, consistent interpretation of the pathogenicity and associated risk for variants in cancer susceptibility genes is essential for effective management of patients and their families. With clinical and laboratory representation from each of the 25 molecular diagnostic laboratories in the UK and ROI, we have established CanVIG-UK (Cancer Variant Interpretation Group UK). Through our monthly […]
Colorectal cancer genetic variants are also associated with serrated polyposis syndrome susceptibility (Contributed by Dr. Sergi Castellví-Bel)
Serrated polyposis syndrome (SPS) is a clinical entity characterized by large and multiple serrated polyps throughout the colon and increased risk for colorectal cancer (CRC). Serrated polyps are considered CRC precursor lesions. Despite recent results in CRC genome-wide studies, the germline predisposition of SPS remains largely unknown. This study is the first to evaluate the […]