Germline structural variant as the cause of Lynch Syndrome in a family from Ecuador
Abstract Colorectal cancer (CRC) is one of the most common cancers worldwide. Lynch Syndrome (LS) is the most common form of hereditary CRC and it is caused by germline defects in the DNA-mismatch repair (MMR) pathway. It is of extreme importance for affected LS patients and their relatives to ident...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-025-00462-y |
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| author | Gemma Llargués-Sistac Laia Bonjoch Jenifer Muñoz Xavier Domínguez-Rovira Teresa Ocaña Maria Isabel Alvarez-Mora Celia Badenas Anna Esteve-Codina Carlos Reyes-Silva Gabriela Jaramillo-Koupermann Maria Teresa Rodrigo Sandra López-Prades Miriam Cuatrecasas Antoni Castells Francesc Balaguer Leticia Moreira Guerau Fernandez Sergi Castellví-Bel |
| author_facet | Gemma Llargués-Sistac Laia Bonjoch Jenifer Muñoz Xavier Domínguez-Rovira Teresa Ocaña Maria Isabel Alvarez-Mora Celia Badenas Anna Esteve-Codina Carlos Reyes-Silva Gabriela Jaramillo-Koupermann Maria Teresa Rodrigo Sandra López-Prades Miriam Cuatrecasas Antoni Castells Francesc Balaguer Leticia Moreira Guerau Fernandez Sergi Castellví-Bel |
| author_sort | Gemma Llargués-Sistac |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) is one of the most common cancers worldwide. Lynch Syndrome (LS) is the most common form of hereditary CRC and it is caused by germline defects in the DNA-mismatch repair (MMR) pathway. It is of extreme importance for affected LS patients and their relatives to identify the germline causative alteration to provide intensified surveillance to those at risk and allow early diagnosis and cancer prevention. Current approaches for LS molecular diagnosis typically involve screening of the MMR genes by targeted gene-panel sequencing and rearrangement screening. We report the identification and characterization of a novel germline structural variant encompassing 48.757 kb, involving the 3’-ends of the MLH1 and LRRFIP2 genes, as the cause of LS in a family of Ecuador. Whole-genome sequencing and transcriptomics allowed the identification of the genomic rearrangement and highlights the importance of the use of these additional approaches to achieve a comprehensive molecular diagnosis in some LS patients. |
| format | Article |
| id | doaj-art-5d91e23c97b8422da27441f4f4caa663 |
| institution | Kabale University |
| issn | 2056-7944 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj-art-5d91e23c97b8422da27441f4f4caa6632025-01-19T12:33:36ZengNature Portfolionpj Genomic Medicine2056-79442025-01-011011610.1038/s41525-025-00462-yGermline structural variant as the cause of Lynch Syndrome in a family from EcuadorGemma Llargués-Sistac0Laia Bonjoch1Jenifer Muñoz2Xavier Domínguez-Rovira3Teresa Ocaña4Maria Isabel Alvarez-Mora5Celia Badenas6Anna Esteve-Codina7Carlos Reyes-Silva8Gabriela Jaramillo-Koupermann9Maria Teresa Rodrigo10Sandra López-Prades11Miriam Cuatrecasas12Antoni Castells13Francesc Balaguer14Leticia Moreira15Guerau Fernandez16Sergi Castellví-Bel17Gastroenterology Deparment, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of BarcelonaGastroenterology Deparment, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of BarcelonaGastroenterology Deparment, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of BarcelonaGastroenterology Deparment, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of BarcelonaGastroenterology Deparment, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of BarcelonaBiochemistry and Molecular Genetics Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red en Enfermedades Raras (CIBERER)Biochemistry and Molecular Genetics Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red en Enfermedades Raras (CIBERER)Centro Nacional de Análisis Genómico (CNAG), University of BarcelonaHospital de Especialidades Eugenio EspejoHospital de Especialidades Eugenio EspejoPathology Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD)Pathology Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD)Pathology Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD)Gastroenterology Deparment, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of BarcelonaGastroenterology Deparment, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of BarcelonaGastroenterology Deparment, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of BarcelonaGenetic and Molecular Medicine-IPER Department, Hospital Sant Joan de Déu, Institut de Recerca Hospital Sant Joan de Déu, Centro de Investigacion Biomedica en Red en Enfermedades Raras (CIBERER), 08950 Esplugues de LlobregatGastroenterology Deparment, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of BarcelonaAbstract Colorectal cancer (CRC) is one of the most common cancers worldwide. Lynch Syndrome (LS) is the most common form of hereditary CRC and it is caused by germline defects in the DNA-mismatch repair (MMR) pathway. It is of extreme importance for affected LS patients and their relatives to identify the germline causative alteration to provide intensified surveillance to those at risk and allow early diagnosis and cancer prevention. Current approaches for LS molecular diagnosis typically involve screening of the MMR genes by targeted gene-panel sequencing and rearrangement screening. We report the identification and characterization of a novel germline structural variant encompassing 48.757 kb, involving the 3’-ends of the MLH1 and LRRFIP2 genes, as the cause of LS in a family of Ecuador. Whole-genome sequencing and transcriptomics allowed the identification of the genomic rearrangement and highlights the importance of the use of these additional approaches to achieve a comprehensive molecular diagnosis in some LS patients.https://doi.org/10.1038/s41525-025-00462-y |
| spellingShingle | Gemma Llargués-Sistac Laia Bonjoch Jenifer Muñoz Xavier Domínguez-Rovira Teresa Ocaña Maria Isabel Alvarez-Mora Celia Badenas Anna Esteve-Codina Carlos Reyes-Silva Gabriela Jaramillo-Koupermann Maria Teresa Rodrigo Sandra López-Prades Miriam Cuatrecasas Antoni Castells Francesc Balaguer Leticia Moreira Guerau Fernandez Sergi Castellví-Bel Germline structural variant as the cause of Lynch Syndrome in a family from Ecuador npj Genomic Medicine |
| title | Germline structural variant as the cause of Lynch Syndrome in a family from Ecuador |
| title_full | Germline structural variant as the cause of Lynch Syndrome in a family from Ecuador |
| title_fullStr | Germline structural variant as the cause of Lynch Syndrome in a family from Ecuador |
| title_full_unstemmed | Germline structural variant as the cause of Lynch Syndrome in a family from Ecuador |
| title_short | Germline structural variant as the cause of Lynch Syndrome in a family from Ecuador |
| title_sort | germline structural variant as the cause of lynch syndrome in a family from ecuador |
| url | https://doi.org/10.1038/s41525-025-00462-y |
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