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Long-read sequencing to resolve the missing heritability in patients suspected o...
Long-read sequencing to resolve the missing heritability in patients suspected of PTEN hamartoma tumour syndrome Individuals with a genetic tumour risk syndrome are at high risk to develop cancer. One of these syndromes is PTEN hamartoma tumour syndrome (PHTS). PHTS is associated with pathogenic variants (PVs) in the PTEN gene. Unfortunately... Individuals with a genetic tumour risk syndrome are at high risk to develop cancer. One of these syndromes is PTEN hamartoma tumour syndrome (PHTS). PHTS is associated with pathogenic variants (PVs) in the PTEN gene. Unfortunately, in the majority of patients suspected of PHTS no PV in PTEN is identified. These patients are considered PHTS-like. The low diagnosis rate in this group of patients suggests the possibility of PVs in regions of PTEN that are not covered in routine diagnostics or suggests that PVs in other genes in the PI3K/AKT/mTOR pathway result in PHTS-like disease. In order to identify the missing heritability in PHTS I aim to develop a long-read sequencing (LRS) approach for PHTS-like patients, which will go beyond the currently state-of-the-art short-read sequencing approaches. I will O1) develop a PTEN-targeted LRS assay and O2) perform this assay on a highly selective cohort of PHTS-like families (n=94). I then will O3) perform whole genome LRS on 25 families that were not solved by targeted LRS to identify novel gene-disease associations. At last, I will O4) validate these new associations in a wider cohort. Via this work, I will improve the diagnostic yield for PHTS by identifying novel genetic mechanisms and genes underlying disease in PHTS-like patients. The unique interdisciplinary structure of the Department of Human Genetics at Radboudumc will allow to rapidly implement genetic testing for the newly identified genetic causes for PHTS. Identification of the precise underlying cause of PHTS will enable cascade genetic testing of at-risk family members to determine their status for the causal variant and thus, risk of disease to them and any future off-spring. Furthermore, this approach will allow the implementation of preventive care strategies for the family members at risk. Overall, my proposal will facilitate a personalized care approach for PHTS(-like) patients and their families for improved clinical outcomes and reduced disease morbidity ver más
14/05/2024
RADBOUDUMC
188K€
Duración del proyecto: 24 meses Fecha Inicio: 2022-04-28
Fecha Fin: 2024-05-14

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-05-14
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2021-PF-01-01: MSCA Postdoctoral Fellowships 2021
Cerrada hace 3 años
Presupuesto El presupuesto total del proyecto asciende a 188K€
Líder del proyecto
STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRU... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5