GERMLINE MUTATIONS IN WNK2 COULD BE ASSOCIATED WITH SERRATED POLYPOSIS SYNDROME, Soares de Lima et al.

Patients with serrated polyposis syndrome (SPS) have multiple and/or large serrated colonic polyps and higher risk for colorectal cancer. Our main aim was to identify the inherited genetic basis of this disease. We performed germline exome sequencing in 39 SPS patients from 16 families and sequenced specific genes in an independent cohort of 211 unrelated […]

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The clinical, neuroimaging, and molecular characteristics of PPP2R5D related neurodevelopmental disorders: an expanded series with functional characterization and genotype-phenotype correlation

Genetics variants in the PPP2R5D gene have been identified to cause a neurodevelopmental disorder characterized by intellectual disabilities, autism spectrum disorder and epilepsy, among others features. Our study, describing 76 individuals, expands the known clinical and molecular spectrum of PPP2R5D related disorders. This allowed us to identify a correlation between groups of variants and their […]

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Identifying the molecular drivers of ALS-implicated missense mutations

Genetic mutations have long been identified as contributors to ALS, however, their molecular-consequences have remained elusive. To address this, we analysed the effects of ALS missense mutations in SOD1, FUS and TDP-43 using in silico tools. FUS and TDP-43 mutations affected disordered regions associated with phase separation and aggregation, while SOD1 mutations destabilized the homodimer, […]

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Prospective validation of the BOADICEA multifactorial breast cancer risk prediction model in a large prospective cohort study

BOADICEA is a multifactorial breast cancer risk model for predicting the future risk of developing breast cancer on the basis of the combined effects of cancer family history, lifestyle, hormonal and reproductive risk factors, mammographic density, polygenic risk score and rare pathogenic variants in all eight established breast cancer susceptibility genes. Here, Yang et al […]

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Enhancing the BOADICEA cancer risk prediction model to incorporate new data on RAD51C, RAD51D, BARD1 updates to tumour pathology and cancer incidence

Pathogenic variants in BARD1, RAD51C and RAD51D have recently been established as breast cancer susceptibility genes; and pathogenic variants in PALB2 have been shown to be associated with epithelial ovarian cancer risk. No cancer risk prediction model currently exists which incorporates these associations. Here, the BOADICEA multifactorial breast and ovarian cancer risk prediction model was […]

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Clinical applicability of the Polygenic Risk Score for breast cancer risk prediction in familial cases

A 313-variant-based polygenic risk score (PRS) is shown to stratify women from breast cancer families into different clinically relevant risk categories. Adding this PRS to family history-based risk prediction would have changed screening advise for 1 out of 3 women diagnosed with breast cancer (BC) at a young age or with a positive family history. […]

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Patient-facing Digital Tools for Delivering Genetic Services: A Systematic Review

Digital tools are used to increase patient access and efficiency in genetic services. We reviewed outcomes of patient-facing digital tools used across the genetic testing journey. Our review found that digital tools can improve patient outcomes and system efficiencies. However, most existing tools are developed for the pre-test phase and cancer setting, limiting our understanding […]

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Systems approach to enhance Lynch syndrome diagnosis through tumour testing

Colorectal cancer tumor testing is recommended to pre-screen patients to determine who should undergo genetic testing to rule out Lynch syndrome, the most common colorectal cancer syndrome. However, compliance is low and most patients with abnormal results do not undergo Lynch syndrome screening. We developed a systems approach that was eventually automated to increase referral for genetic […]

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Clinical diversity and molecular mechanism of VPS35L-associated Ritscher-Schinzel syndrome

The Retriever subunit VPS35L is the third responsible gene for Ritscher-Schinzel syndrome (RSS) after WASHC5 and CCDC22. To date, only one pair of siblings have been reported and their condition was significantly more severe than typical RSS. This report expands the clinical spectrum of patients with pathogenic VPS35L variants, and identifies both overlapping and distinctive features […]

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Advancing in Schaaf-Yang syndrome pathophysiology: from bedside to subcellular analyses of truncated MAGEL2

Truncating mutations in MAGEL2, which lead to a shortened protein, cause Schaaf-Yang syndrome (SYS). We have compiled all reported cases and provide Clinical Management Recommendations to help families and physicians manage these patients. We have further characterized the cellular effects of these mutations. We have introduced a normal (full) or truncated form of the gene […]

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