{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Horti-Oravecz K"],"funding":["Magyar Tudományos Akadémia (Hungarian Academy of Sciences)"],"pagination":["5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11742971"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(1)"],"pubmed_abstract":["Multigene panel tests (MGPTs) revolutionized the diagnosis of Lynch syndrome (LS), however noncoding pathogenic variants (PVs) can only be detected by complementary methods including whole genome sequencing (WGS). Here we present a DNA-, RNA- and tumor tissue-based WGS prioritization workflow for patients with a suspicion of LS where MGPT detected no LS-related PV. Among the 100 enrolled patients, MGPT detected 28 simple PVs and an additional 3 complex PVs. Among the 69 MGPT-negative patients, the lack of somatic MLH1 promoter methylation in a patient with a distinguished MLH1 allelic imbalance selected this sample for WGS. This returned a germline deep intronic MLH1 variant, with further functional studies confirming its' pathogenicity. Interestingly, all three complex PVs and the MLH1 de"],"journal":["NPJ genomic medicine"],"pubmed_title":["Whole genome sequencing completes the molecular genetic testing workflow of patients with Lynch syndrome."],"pmcid":["PMC11742971"],"funding_grant_id":["BO/00141/21","Bolyai Research Fellowship"],"pubmed_authors":["Liko I","Rusnakova D","Vereczkey I","Butz H","Olah E","Horti-Oravecz K","Patocs A","Strausz T","Szemes T","Papp J","Pocza T","Sedlackova T","Grolmusz VK","Toth E","Bozsik A"],"additional_accession":[]},"is_claimable":false,"name":"Whole genome sequencing completes the molecular genetic testing workflow of patients with Lynch syndrome.","description":"Multigene panel tests (MGPTs) revolutionized the diagnosis of Lynch syndrome (LS), however noncoding pathogenic variants (PVs) can only be detected by complementary methods including whole genome sequencing (WGS). Here we present a DNA-, RNA- and tumor tissue-based WGS prioritization workflow for patients with a suspicion of LS where MGPT detected no LS-related PV. Among the 100 enrolled patients, MGPT detected 28 simple PVs and an additional 3 complex PVs. Among the 69 MGPT-negative patients, the lack of somatic MLH1 promoter methylation in a patient with a distinguished MLH1 allelic imbalance selected this sample for WGS. This returned a germline deep intronic MLH1 variant, with further functional studies confirming its' pathogenicity. Interestingly, all three complex PVs and the MLH1 de","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2025-04-22T10:28:32.747Z","creation":"2025-04-05T23:34:31.094Z"},"accession":"S-EPMC11742971","cross_references":{"pubmed":["39827169"],"doi":["10.1038/s41525-025-00461-z"]}}