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 […]
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Identifying novel oncogenic RET mutations and characterising their sensitivity to RET-specific inhibitors
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
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
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
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
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
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 […]
Diverse types of genomic evidence converge on alcohol use disorder risk genes
Alcohol use disorder (AUD) is one of the most common forms of substance use disorders. Genome-wide association studies (GWAS) have identified a number of AUD-associated variants, including those in alcohol metabolism genes. It is important to understand where and how these genetic variants may modulate gene expression, making individuals more vulnerable to AUD. In this […]
Clinical and genetic features of somatic mosaicism in facioscapulohumeral dystrophy
Facioscapulohumeral dystrophy (FSHD), one of the most common adult muscular diseases, shows significant clinical heterogeneity that can be partially explained by somatic mosaicism. We here report our findings from the prospective, hospital-based, case-control, observational study of 35 mosaic FSHD patients recruited over 10 years. This largest-to-date mosaic FSHD cohort exhibited significant clinical heterogeneity and relatively […]
Bi-allelic variants in MAATS1 encoding CFAP91, a calmodulin- and spoke-associated complex protein, cause severe astheno-teratozoospermia and male infertility
Multiple morphological abnormalities of the sperm flagella (MMAF) consistently lead to male infertility due to a reduced or absent sperm motility. Despite numerous genes described to be associated with MMAF, more than half of the cases analyzed remain unresolved, suggesting that many yet uncharacterized gene defects account for this phenotype. In this study, we identified […]