Publications by authors named "S Aretz"
Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.
View Article and Find Full Text PDFArticle Synopsis
- - Pathogenic variants in the APC gene are responsible for familial adenomatous polyposis, the most common hereditary gastrointestinal polyposis syndrome, prompting the development of specific classification criteria to aid in variant interpretation.
- - The study involved applying these APC-specific criteria to assess over 10,000 unique APC variants from databases like ClinVar and LOVD, leading to a significant reclassification of variants of uncertain significance (VUSs), with many being reassessed as (likely) benign or (likely) pathogenic.
- - The results showed that using these tailored criteria effectively reduced VUSs by 37%, highlighted the potential for systematic variant classification in large datasets, and established a model that could benefit future genetic variant interpretation efforts in
Article Synopsis
- The study focused on improving the classification of genetic variants linked to familial adenomatous polyposis using APC-specific criteria developed by an expert panel.
- A total of 10,228 unique variants were analyzed, resulting in 41% of VUS from ClinVar and 61% from LOVD being reclassified, primarily as (Likely) Benign, which reduced the overall VUS by 37%.
- The research highlighted a systematic approach to variant classification in large datasets that could be applied to other gene/disease interpretations and allowed for prioritization of VUS requiring further evidence collection.
Background: Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers.
Methods: A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added.
Lynch syndrome (LS; HNPCC) patients carry heterozygous pathogenic germline variants in mismatch repair (MMR) genes, which have also been shown to play an important role in meiosis. Therefore, it was hypothesized, that LS might be associated with a higher risk for premature ovarian failure (POF) or earlier menopause. Data on medical gynaecological history, cancer diagnoses and therapy were collected from 167 female LS patients and compared to a population-based control cohort.
View Article and Find Full Text PDF