Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness
Purpose Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better unders...
| Autores: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p6184 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6184 |
| Access Level: | acceso abierto |
| Palabra clave: | next-generation sequencing targeted exome analysis neuromuscular disease limb-girdle weakness genetic diagnosis |
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Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weaknessTopf, AJohnson, KBates, APhillips, LChao, KREngland, EMLaricchia, KMMullen, TValkanas, EXu, LWBertoli, MBlain, ACasasus, ABDuff, JMroczek, MSpecht, SLek, MEnsini, MMacArthur, DGStraub, VAlonso-Pérez J.González-Quereda L.next-generation sequencingtargeted exome analysisneuromuscular diseaselimb-girdle weaknessgenetic diagnosisPurpose Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. Methods Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. Results We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants inCAPN3,DYSF,ANO5,DMD,RYR1,TTN,COL6A2, andSGCAcollectively accounted for over half of the solved cases; while variants in newer disease genes, such asBVESandPOGLUT1, were also found. The remaining well-characterized unsolved patients (48%) need further investigation. Conclusion Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes.SPRINGERNATURE2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6184GENETICS IN MEDICINEISSN: 10983600ISSNe: 15300366reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p61842026-06-14T12:41:47Z |
| dc.title.none.fl_str_mv |
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness |
| title |
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness |
| spellingShingle |
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness Topf, A next-generation sequencing targeted exome analysis neuromuscular disease limb-girdle weakness genetic diagnosis |
| title_short |
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness |
| title_full |
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness |
| title_fullStr |
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness |
| title_full_unstemmed |
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness |
| title_sort |
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness |
| dc.creator.none.fl_str_mv |
Topf, A Johnson, K Bates, A Phillips, L Chao, KR England, EM Laricchia, KM Mullen, T Valkanas, E Xu, LW Bertoli, M Blain, A Casasus, AB Duff, J Mroczek, M Specht, S Lek, M Ensini, M MacArthur, DG Straub, V Alonso-Pérez J. González-Quereda L. |
| author |
Topf, A |
| author_facet |
Topf, A Johnson, K Bates, A Phillips, L Chao, KR England, EM Laricchia, KM Mullen, T Valkanas, E Xu, LW Bertoli, M Blain, A Casasus, AB Duff, J Mroczek, M Specht, S Lek, M Ensini, M MacArthur, DG Straub, V Alonso-Pérez J. González-Quereda L. |
| author_role |
author |
| author2 |
Johnson, K Bates, A Phillips, L Chao, KR England, EM Laricchia, KM Mullen, T Valkanas, E Xu, LW Bertoli, M Blain, A Casasus, AB Duff, J Mroczek, M Specht, S Lek, M Ensini, M MacArthur, DG Straub, V Alonso-Pérez J. González-Quereda L. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
next-generation sequencing targeted exome analysis neuromuscular disease limb-girdle weakness genetic diagnosis |
| topic |
next-generation sequencing targeted exome analysis neuromuscular disease limb-girdle weakness genetic diagnosis |
| description |
Purpose Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. Methods Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. Results We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants inCAPN3,DYSF,ANO5,DMD,RYR1,TTN,COL6A2, andSGCAcollectively accounted for over half of the solved cases; while variants in newer disease genes, such asBVESandPOGLUT1, were also found. The remaining well-characterized unsolved patients (48%) need further investigation. Conclusion Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6184 |
| url |
https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6184 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
SPRINGERNATURE |
| publisher.none.fl_str_mv |
SPRINGERNATURE |
| dc.source.none.fl_str_mv |
GENETICS IN MEDICINE ISSN: 10983600 ISSNe: 15300366 reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| collection |
r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
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15,812455 |