Pathogenic variants in TNRC6B cause a genetic disorder characterised by developmental delay/intellectual disability and a spectrum of neurobehavioural phenotypes including autism and ADHD

We report a new genetic disorder in 17 patients characterized by developmental delay especially in their speech, a variable degree of intellectual disability, decreased muscle tone, as well as neurobehavioral difficulties including autism and Attention Deficit and Hyperactivity Disorder. All patients have genetic variants in a gene called TNRC6B, which is important for the regulation […]

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Severity of oro-dental anomalies in Loeys-Dietz syndrome segregates by gene mutation

Rare diseases that have multisystemic involvements often feature oral and dental manifestations that are overlooked even though they may significantly affect patients’ quality of life. In this study, we thoroughly characterized the oro-dental anomalies in Loeys-Dietz syndrome, a rare disorder affecting the cardiovascular system. The most frequent anomalies include abnormal palate, short mandible and tooth […]

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Association between genetic polymorphisms and endometrial cancer risk: a systematic review

Single nucleotide polymorphisms (SNPs) are differences in single building blocks of DNA between individuals. Hundreds of SNPs have been shown to influence susceptibility to disease and response to treatment. In this paper, we systematically reviewed the literature to identify SNPs that contribute to endometrial cancer risk. We report 24 SNPs of highest significance, and no […]

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RE-DEFINITION OF FAMILIAL INTESTINAL GASTRIC CANCER: CLINICAL AND GENETIC PERSPECTIVES

Familial Intestinal Gastric Cancer (FIGC) remains genetically unexplained and poorly characterized, preventing the design of testing criteria for genetic diagnosis. We analyzed family trees from FIGC families and compared their tumour and normal genetic profiles with those of sporadic stomach cancer patients. We found that FIGC families present 2 or more stomach cancers, but may […]

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MicroRNA-4516-mediated regulation of MAPK10 relies on 3’UTR cis-acting variants and contributes to the altered risk of Hirschsprung disease

Hirschsprung disease (HSCR) is a life-threatening genetic disorder in which the enteric nervous system (ENS) is completely missing from the distal gut. However, the contribution of genetic factors to HSCR remains unclear. In this paper, we identify MAPK10 as a HSCR susceptibility gene, which is directly regulated by miR-4516, and interestingly, the regulatory mechanism is […]

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Investigating the genetic susceptibility to exertional heat illness

Some people show an increased propensity to develop heat illness, rhabdomyolysis (muscle tissue breakdown) or both following heavy exercise suggesting a genetic contribution. Variants in a number of genes, including RYR1 are associated with rhabdomyolysis but the situation with exertional heat illness is less certain. We found potentially pathogenic (disease-related) variants in 20 genes in […]

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Phenotype of genetically confirmed Silver-Russell syndrome beyond childhood

Silver Russell syndrome (SRS) is a rare disorder affecting growth and behaviour, caused by faults in the biological control of growth factors vital to early development. We studied the medical history of 33 older people with SRS. 60% had significantly reduced height, though 70% had received treatment; this suggests a need for improved intervention. In […]

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Excess of singleton loss-of-function variants in Parkinson’s disease contributes to genetic risk

Parkinson’s disease (PD) is a complex neurodegenerative disorder. Several risk variants and genes were identified by genetic studies and predictive disease risk models were built based on associations with common variants. We showed that singleton loss-of-function variants contribute to the genetic architecture of PD and that disease risk prediction models combining singleton and common variants […]

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CDK5RAP2 primary microcephaly is associated with hypothalamic, retinal and cochlear developmental defects

Primary Microcephaly (PM) is a neurodevelopmental disorder characterized by a small brain size frequently associated with intellectual disability. CDK5RAP2 is a cyclin-dependent kinase regulatory subunit associated protein whose deficiency causes a rare recessive isolated PM called MCPH3. In this article, Nasser and colleagues report patients carrying new bi-allelic CDK5RAP2 mutations and found that all patients […]

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ATR-16 syndrome: mechanisms linking monosomy to phenotype

Advances in DNA sequencing technology mean chromosomal deletions are increasingly found in healthy individuals and also in patients with a wide range of developmental abnormalities. Understanding the contribution of each deletion to the clinical picture is challenging. In this work, as an example of this common phenomenon, we analysed 41 patients with simple deletions of […]

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