Complete loss of the X-linked gene CASK causes severe cerebellar degeneration

X-linked disorders like CASK-linked pontocerebellar hypoplasia and Rett syndrome, predominantly affecting girls, are presumed to be neurodevelopmental disorders. Here, by performing a detailed analysis of a boy without CASK and genetically ablating CASK from cerebellar neurons in mice, we demonstrate that CASK loss does not affect neuronal or brain development. Instead, CASK loss results in […]

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Disorders and roles of tsRNA, snoRNA, snRNA and piRNA in cancer

Non-coding RNAs are a large-scale and alloplasmatic family of RNAs. According to their size, small non-coding RNAs are approximately 18-200 nt. In recent years, increasing evidence has shown that small non-coding RNAs such as tsRNA, snoRNA, snRNA and piRNA play important roles in many biological processes, and their dysregulation is closely related to cancer progression. […]

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RNA splicing analysis contributes to reclassifying variants of uncertain significance and improves the diagnosis of monogenic disorders

Routinely used Whole Exome Sequencing (WES) in genetic diagnosis for monogenic disorders revealed numerous variants of uncertain significance (VUSs), which poses considerable problems for genetic counselling and clinical management. In fact, many disease-causing variants have been reported to resulting in aberrant gene splicing. Therefore, for VUSs suspected to cause aberrant splicing, additional evidence can be […]

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Dominant negative mutation in oxalate transporter SLC26A6 associated with enteric hyperoxaluria and nephrolithiasis

Nephrolithiasis results from interaction between genetic and environmental factors. Calcium oxalate is the most common type of kidney stone. We report a novel genetic mechanism causing hyperoxaluria and nephrolithiasis. In one family, we detected a mutation within the SLC26A6 gene that encodes an oxalate transporter. This mutation impairs SLC26A6 function, which normally secretes oxalate in […]

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Simplified and more sensitive criteria for identifying individuals with pathogenic CDH1 variants

Individuals carrying mutations in the CDH1 gene have a high likelihood of developing stomach cancer (lifetime risk 24-42%) and breast cancer (lifetime risk about 43-55%). Identification of these individuals through genetic testing is important because these cancers can be prevented by prophylactic surgery or detected early with endoscopy and breast imaging. Current guidelines recommend genetic testing when […]

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Long term dormancy in a BRCA1 heterozygote

Germline pathogenic variants in BRCA1 or BRCA2 genes increase the risk of ovarian high grade serous carcinoma, the most common and most lethal subtype of epithelial ovarian cancer. Carriers of these genetic variants are usually offered surgery known as risk-reducing salpingo-oophorectomy (RRSO) where the Fallopian tubes and ovaries are removed. We report the case of […]

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CDH1 germline mutations in healthy individuals from families with the hereditary diffuse gastric cancer syndrome

Hereditary diffuse gastric cancer is an inherited cancer predisposition syndrome associated with CDH1 germline mutations. To date, more than 500 mutations are described from different countries, with a particular higher mutation frequency in countries with low incidence for gastric cancer. The distribution of germline mutations sub-types in this inherited cancer susceptibility is rather heterogeneous: missense […]

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Impaired social cognition and fine dexterity in patients with Cowden syndrome associated with germline PTEN variants

Cowden syndrome is a genetic disorder related to germline PTEN variants and characterized by increased risk of cancers. These patients sometimes show behaviors considered as maladapted to social norms and conventions. We collected data on 15 patients from a single center in France. We analyzed their abilities in social cognition, considered as cognitive processes involved […]

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Multimodal bioinformatic analyses of the neurodegenerative disease-associated TECPR2 gene reveal its diverse roles

Loss of TECPR2 function has been implicated in an array of neurodegenerative diseases, but what exactly is that function? Understanding TECPR2 function is essential for developing precision diagnostics and targeted treatment options for TECPR2-related neurodegenerative diseases. Therefore, we leveraged the increasing amounts of functional genomic data to perform a first comprehensive functional characterization of TECPR2. We report that TECPR2 might […]

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