Genome sequencing in families with congenital limb malformations

  1. Elsner, Jonas
  2. Mensah, Martin A.
  3. Holtgrewe, Manuel
  4. Hertzberg, Jakob
  5. Bigoni, Stefania
  6. Busche, Andreas
  7. Coutelier, Marie
  8. de Silva, Deepthi C.
  9. Elçioglu, Nursel
  10. Filges, Isabel
  11. Gerkes, Erica
  12. Girisha, Katta M.
  13. Graul-Neumann, Luitgard
  14. Jamsheer, Aleksander
  15. Krawitz, Peter
  16. Kurth, Ingo
  17. Markus, Susanne
  18. Megarbane, Andre
  19. Reis, André
  20. Reuter, Miriam S.
  21. Svoboda, Daniel
  22. Teller, Christopher
  23. Tuysuz, Beyhan
  24. Türkmen, Seval
  25. Wilson, Meredith
  26. Woitschach, Rixa
  27. Vater, Inga
  28. Caliebe, Almuth
  29. Hülsemann, Wiebke
  30. Horn, Denise
  31. Mundlos, Stefan
  32. Spielmann, Malte

Download
s00439-021-02295-y.pdf 7,14MB
WeightNameValue
1000 Titel
  • Genome sequencing in families with congenital limb malformations
1000 Autor/in
  1. Elsner, Jonas |
  2. Mensah, Martin A. |
  3. Holtgrewe, Manuel |
  4. Hertzberg, Jakob |
  5. Bigoni, Stefania |
  6. Busche, Andreas |
  7. Coutelier, Marie |
  8. de Silva, Deepthi C. |
  9. Elçioglu, Nursel |
  10. Filges, Isabel |
  11. Gerkes, Erica |
  12. Girisha, Katta M. |
  13. Graul-Neumann, Luitgard |
  14. Jamsheer, Aleksander |
  15. Krawitz, Peter |
  16. Kurth, Ingo |
  17. Markus, Susanne |
  18. Megarbane, Andre |
  19. Reis, André |
  20. Reuter, Miriam S. |
  21. Svoboda, Daniel |
  22. Teller, Christopher |
  23. Tuysuz, Beyhan |
  24. Türkmen, Seval |
  25. Wilson, Meredith |
  26. Woitschach, Rixa |
  27. Vater, Inga |
  28. Caliebe, Almuth |
  29. Hülsemann, Wiebke |
  30. Horn, Denise |
  31. Mundlos, Stefan |
  32. Spielmann, Malte |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-06-22
1000 Erschienen in
1000 Quellenangabe
  • 140(8):1229-1239
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00439-021-02295-y |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263393/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • The extensive clinical and genetic heterogeneity of congenital limb malformation calls for comprehensive genome-wide analysis of genetic variation. Genome sequencing (GS) has the potential to identify all genetic variants. Here we aim to determine the diagnostic potential of GS as a comprehensive one-test-for-all strategy in a cohort of undiagnosed patients with congenital limb malformations. We collected 69 cases (64 trios, 1 duo, 5 singletons) with congenital limb malformations with no molecular diagnosis after standard clinical genetic testing and performed genome sequencing. We also developed a framework to identify potential noncoding pathogenic variants. We identified likely pathogenic/disease-associated variants in 12 cases (17.4%) including four in known disease genes, and one repeat expansion in HOXD13. In three unrelated cases with ectrodactyly, we identified likely pathogenic variants in UBA2, establishing it as a novel disease gene. In addition, we found two complex structural variants (3%). We also identified likely causative variants in three novel high confidence candidate genes. We were not able to identify any noncoding variants. GS is a powerful strategy to identify all types of genomic variants associated with congenital limb malformation, including repeat expansions and complex structural variants missed by standard diagnostic approaches. In this cohort, no causative noncoding SNVs could be identified.
1000 Sacherschließung
lokal Transcription Factors/genetics [MeSH]
lokal Limb Deformities, Congenital/metabolism [MeSH]
lokal Molecular Medicine
lokal Gene Expression [MeSH]
lokal Cohort Studies [MeSH]
lokal Genetic Testing [MeSH]
lokal Original Investigation
lokal Limb Deformities, Congenital/pathology [MeSH]
lokal Infant [MeSH]
lokal Male [MeSH]
lokal Base Sequence [MeSH]
lokal Human Genetics
lokal Transcription Factors/deficiency [MeSH]
lokal Mutation [MeSH]
lokal Whole Genome Sequencing [MeSH]
lokal Humans [MeSH]
lokal Genetic Heterogeneity [MeSH]
lokal Homeodomain Proteins/genetics [MeSH]
lokal DNA Copy Number Variations [MeSH]
lokal Pedigree [MeSH]
lokal Metabolic Diseases
lokal Ubiquitin-Activating Enzymes/deficiency [MeSH]
lokal Gene Function
lokal Ubiquitin-Activating Enzymes/genetics [MeSH]
lokal Limb Deformities, Congenital/genetics [MeSH]
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/RWxzbmVyLCBKb25hcw==|https://frl.publisso.de/adhoc/uri/TWVuc2FoLCBNYXJ0aW4gQS4=|https://frl.publisso.de/adhoc/uri/SG9sdGdyZXdlLCBNYW51ZWw=|https://frl.publisso.de/adhoc/uri/SGVydHpiZXJnLCBKYWtvYg==|https://frl.publisso.de/adhoc/uri/Qmlnb25pLCBTdGVmYW5pYQ==|https://frl.publisso.de/adhoc/uri/QnVzY2hlLCBBbmRyZWFz|https://frl.publisso.de/adhoc/uri/Q291dGVsaWVyLCBNYXJpZQ==|https://frl.publisso.de/adhoc/uri/ZGUgU2lsdmEsIERlZXB0aGkgQy4=|https://frl.publisso.de/adhoc/uri/RWzDp2lvZ2x1LCBOdXJzZWw=|https://frl.publisso.de/adhoc/uri/RmlsZ2VzLCBJc2FiZWw=|https://frl.publisso.de/adhoc/uri/R2Vya2VzLCBFcmljYQ==|https://frl.publisso.de/adhoc/uri/R2lyaXNoYSwgS2F0dGEgTS4=|https://frl.publisso.de/adhoc/uri/R3JhdWwtTmV1bWFubiwgTHVpdGdhcmQ=|https://frl.publisso.de/adhoc/uri/SmFtc2hlZXIsIEFsZWtzYW5kZXI=|https://frl.publisso.de/adhoc/uri/S3Jhd2l0eiwgUGV0ZXI=|https://frl.publisso.de/adhoc/uri/S3VydGgsIEluZ28=|https://frl.publisso.de/adhoc/uri/TWFya3VzLCBTdXNhbm5l|https://frl.publisso.de/adhoc/uri/TWVnYXJiYW5lLCBBbmRyZQ==|https://frl.publisso.de/adhoc/uri/UmVpcywgQW5kcsOp|https://frl.publisso.de/adhoc/uri/UmV1dGVyLCBNaXJpYW0gUy4=|https://frl.publisso.de/adhoc/uri/U3ZvYm9kYSwgRGFuaWVs|https://frl.publisso.de/adhoc/uri/VGVsbGVyLCBDaHJpc3RvcGhlcg==|https://frl.publisso.de/adhoc/uri/VHV5c3V6LCBCZXloYW4=|https://frl.publisso.de/adhoc/uri/VMO8cmttZW4sIFNldmFs|https://frl.publisso.de/adhoc/uri/V2lsc29uLCBNZXJlZGl0aA==|https://frl.publisso.de/adhoc/uri/V29pdHNjaGFjaCwgUml4YQ==|https://frl.publisso.de/adhoc/uri/VmF0ZXIsIEluZ2E=|https://frl.publisso.de/adhoc/uri/Q2FsaWViZSwgQWxtdXRo|https://frl.publisso.de/adhoc/uri/SMO8bHNlbWFubiwgV2llYmtl|https://frl.publisso.de/adhoc/uri/SG9ybiwgRGVuaXNl|https://frl.publisso.de/adhoc/uri/TXVuZGxvcywgU3RlZmFu|https://frl.publisso.de/adhoc/uri/U3BpZWxtYW5uLCBNYWx0ZQ==
1000 Hinweis
  • DeepGreen-ID: 5c67556d93b845649b5b5b6d2cf1dc64 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
1000 Label
1000 Dateien
  1. Genome sequencing in families with congenital limb malformations
    Genome sequencing in families with congenital limb malformations
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6446834.rdf
1000 Erstellt am 2023-04-28T14:18:36.271+0200
1000 Erstellt von 322
1000 beschreibt frl:6446834
1000 Zuletzt bearbeitet Fri Oct 20 19:05:37 CEST 2023
1000 Objekt bearb. Fri Oct 20 19:05:37 CEST 2023
1000 Vgl. frl:6446834
1000 Oai Id
  1. oai:frl.publisso.de:frl:6446834 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source