Many cases of familial renal cell carcinoma (RCC) are unexplained by mutations in known predisposing genes or shared environmental factors. We have shown that PBRM1, a tumor supressor gene with frequent somatic mutations in clear cell RCC, is also a RCC susceptibility gene. Indeed, four members from the same family, all with a history of […]
Latest articles
Prevalence of MLH1 constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer
Lynch syndrome is a hereditary condition which predispose to colorectal cancer and other tumors. A particular cause of this syndrome is the MLH1 constitutional methylation (epimutation). Universal tumor testing is recommended as the best strategy to identify Lynch syndrome patients. This screening renders a considerable number of cases with MLH1 methylation in tumors raising the […]
Canadian Open Genetics Repository (COGR): a unified clinical genomics database as a community resource for standardising and sharing genetic interpretations
Genomic medicine is still an emerging field. Scientists working at different institutions have developed naming systems and checklists and specialized databases that differ significantly from one to another; their utility is compromised by the many differences between them. The result is that sharing such data across the biomedical community has been difficult if not impossible. […]
Loss-of-function de novo mutations play an important role in severe human neural tube defects
Neural tube defects (NTDs) are very common and severe birth malformations that are caused by failure of neural tube closure. They are caused by a combination of genetic and environmental factors that remain largely unknown. Anencephaly and spina bifida are severe NTDs that affect reproductive fitness but are still prevalent across generations, suggesting a role […]
Familial periventricular nodular heterotopia, epilepsy and Melnick-Needles Syndrome caused by a single FLNA mutation with combined gain-of-function and loss-of-function effects
Loss-of-function mutations of the FLNA gene cause X-linked periventricular nodular heterotopia (PNH) while gain-of-function mutations cause the Otopalatodigital (OPD) spectrum. These two conditions are known to be mutually exclusive phenotypes. We describe a family in which a woman and her three daughters exhibited a phenotype combining PNH, epilepsy and Melnick-Needles syndrome, a skeletal disorder assigned […]
A novel syndrome of Klippel-Feil anomaly, myopathy, and characteristic facies is linked to a null mutation in MYO18B
Klippel-Feil anomaly (KFA) is a rare disorder encompassing fusion of the cervical spine, as well as low posterior hair line and limited neck mobility. Here we describe a mutation in a novel gene, MYO18B, which results in KFA along with muscular weakness. This is an association that has never been reported before. High resolution microscopy […]
Bilateral vestibular schwannomas in older patients: NF2 or chance?
We have previously estimated that one in two million people will develop bilateral vestibular schwannomas by chance. We show for the first time molecular proof that a man who developed bilateral vestibular schwannomas aged 52 and 67 years of age had developed these by independent events in the NF2 gene with no evidence of a […]
A homozygous PMS2 founder mutation with an attenuated constitutional mismatch repair deficiency phenotype
The recent discovery of a new mutation in the DNA mismatch repair gene PMS2 that is recurrent in the Inuit population surrounding Hudson Bay, Canada offers new insights suggesting that even a small, residual function of the gene in patients is sufficient to delay the age of onset of tumours. This new finding adds to […]
BRCA1 Circos: a visualisation resource for functional analysis of missense variants
Carriers of germline pathogenic variants in BRCA1 have a significantly increased risk of breast and ovarian cancers. However, genetic testing may also uncover a variant of unknown significance (VUS). Due to the rarity of these variants clinical and family data are usually lacking to determine cancer risk association. Functional assays can be used to assess […]
Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing
Learning outcomes After completing this module you should be able to: Be aware of the genetic heterogeneity of ID and the diagnostic yield of different approaches to investigation Understand the challenges associated with interpreting variants identified by next generation sequencing (NGS) and the principles behind assigning causality Understand the strengths and weaknesses of a targeted […]