Missense and truncating variants in CHD5 in a dominant neurodevelopmental disorder with intellectual disability, behavioral disturbances, and epilepsy

  1. Parenti, Ilaria ORCID logo
  2. Lehalle, Daphné ORCID logo
  3. Nava, Caroline ORCID logo
  4. Torti, Erin ORCID logo
  5. Leitão, Elsa ORCID logo
  6. Person, Richard
  7. Mizuguchi, Takeshi ORCID logo
  8. Matsumoto, Naomichi ORCID logo
  9. Kato, Mitsuhiro ORCID logo
  10. Nakamura, Kazuyuki ORCID logo
  11. de Man, Stella ORCID logo
  12. Cope, Heidi ORCID logo
  13. Shashi, Vandana
  14. Friedman, Jennifer
  15. Joset, Pascal
  16. Steindl, Katharina
  17. Rauch, Anita ORCID logo
  18. Muffels, Irena
  19. van Hasselt, Peter M ORCID logo
  20. petit, florence ORCID logo
  21. Smol, Thomas ORCID logo
  22. Le Guyader, Gwenaël
  23. Bilan, Frédéric ORCID logo
  24. Sorlin, Arthur ORCID logo
  25. Vitobello, Antonio ORCID logo
  26. PHILIPPE, Christophe ORCID logo
  27. van de Laar, Ingrid ORCID logo
  28. van Slegtenhorst, Marjon A.
  29. Campeau, Philippe ORCID logo
  30. Au, Ping Yee ORCID logo
  31. Nakashima, Mitsuko ORCID logo
  32. Saitsu, Hirotomo ORCID logo
  33. Yamamoto, Tatsuya ORCID logo
  34. Nomura, Yumiko
  35. Louie, Raymond ORCID logo
  36. Lyons, Michael ORCID logo
  37. Dobson, Amy
  38. Plomp, Astrid S.
  39. Motazacker, M. Mahdi
  40. Kaiser, Frank J.
  41. Timberlake, Andrew ORCID logo
  42. Fuchs, Sabine ORCID logo
  43. Depienne, Christel ORCID logo
  44. Mignot, Cyril ORCID logo

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1000 Titel
  • Missense and truncating variants in CHD5 in a dominant neurodevelopmental disorder with intellectual disability, behavioral disturbances, and epilepsy
1000 Autor/in
  1. Parenti, Ilaria |
  2. Lehalle, Daphné |
  3. Nava, Caroline |
  4. Torti, Erin |
  5. Leitão, Elsa |
  6. Person, Richard |
  7. Mizuguchi, Takeshi |
  8. Matsumoto, Naomichi |
  9. Kato, Mitsuhiro |
  10. Nakamura, Kazuyuki |
  11. de Man, Stella |
  12. Cope, Heidi |
  13. Shashi, Vandana |
  14. Friedman, Jennifer |
  15. Joset, Pascal |
  16. Steindl, Katharina |
  17. Rauch, Anita |
  18. Muffels, Irena |
  19. van Hasselt, Peter M |
  20. petit, florence |
  21. Smol, Thomas |
  22. Le Guyader, Gwenaël |
  23. Bilan, Frédéric |
  24. Sorlin, Arthur |
  25. Vitobello, Antonio |
  26. PHILIPPE, Christophe |
  27. van de Laar, Ingrid |
  28. van Slegtenhorst, Marjon A. |
  29. Campeau, Philippe |
  30. Au, Ping Yee |
  31. Nakashima, Mitsuko |
  32. Saitsu, Hirotomo |
  33. Yamamoto, Tatsuya |
  34. Nomura, Yumiko |
  35. Louie, Raymond |
  36. Lyons, Michael |
  37. Dobson, Amy |
  38. Plomp, Astrid S. |
  39. Motazacker, M. Mahdi |
  40. Kaiser, Frank J. |
  41. Timberlake, Andrew |
  42. Fuchs, Sabine |
  43. Depienne, Christel |
  44. Mignot, Cyril |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-05-04
1000 Erschienen in
1000 Quellenangabe
  • 140(7):1109-1120
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00439-021-02283-2 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197709/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Located in the critical 1p36 microdeletion region, the chromodomain helicase DNA-binding protein 5 (CHD5) gene encodes a subunit of the nucleosome remodeling and deacetylation (NuRD) complex required for neuronal development. Pathogenic variants in six of nine chromodomain (CHD) genes cause autosomal dominant neurodevelopmental disorders, while CHD5-related disorders are still unknown. Thanks to GeneMatcher and international collaborations, we assembled a cohort of 16 unrelated individuals harboring heterozygous CHD5 variants, all identified by exome sequencing. Twelve patients had de novo CHD5 variants, including ten missense and two splice site variants. Three familial cases had nonsense or missense variants segregating with speech delay, learning disabilities, and/or craniosynostosis. One patient carried a frameshift variant of unknown inheritance due to unavailability of the father. The most common clinical features included language deficits (81%), behavioral symptoms (69%), intellectual disability (64%), epilepsy (62%), and motor delay (56%). Epilepsy types were variable, with West syndrome observed in three patients, generalized tonic-clonic seizures in two, and other subtypes observed in one individual each. Our findings suggest that, in line with other CHD-related disorders, heterozygous CHD5 variants are associated with a variable neurodevelopmental syndrome that includes intellectual disability with speech delay, epilepsy, and behavioral problems as main features.
1000 Sacherschließung
lokal Adolescent [MeSH]
lokal Female [MeSH]
lokal Catalytic Domain [MeSH]
lokal Humans [MeSH]
lokal Intellectual Disability/genetics [MeSH]
lokal Genes, Dominant [MeSH]
lokal Molecular Medicine
lokal Neurodevelopmental Disorders/physiopathology [MeSH]
lokal Nerve Tissue Proteins/genetics [MeSH]
lokal Mutation, Missense [MeSH]
lokal Neurodevelopmental Disorders/genetics [MeSH]
lokal Cohort Studies [MeSH]
lokal DNA Helicases/genetics [MeSH]
lokal Intellectual Disability/physiopathology [MeSH]
lokal Original Investigation
lokal Pedigree [MeSH]
lokal Male [MeSH]
lokal Metabolic Diseases
lokal Young Adult [MeSH]
lokal Gene Function
lokal Child [MeSH]
lokal Epilepsy/genetics [MeSH]
lokal Child, Preschool [MeSH]
lokal Human Genetics
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-1825-6237|https://orcid.org/0000-0002-2193-8685|https://orcid.org/0000-0003-1272-0518|https://orcid.org/0000-0001-5790-1051|https://orcid.org/0000-0001-5051-9714|https://frl.publisso.de/adhoc/uri/UGVyc29uLCBSaWNoYXJk|https://orcid.org/0000-0003-4998-1244|https://orcid.org/0000-0001-9846-6500|https://orcid.org/0000-0003-1485-8553|https://orcid.org/0000-0003-0266-9341|https://orcid.org/0000-0002-3895-4649|https://orcid.org/0000-0003-0586-9277|https://frl.publisso.de/adhoc/uri/U2hhc2hpLCBWYW5kYW5h|https://frl.publisso.de/adhoc/uri/RnJpZWRtYW4sIEplbm5pZmVy|https://frl.publisso.de/adhoc/uri/Sm9zZXQsIFBhc2NhbA==|https://frl.publisso.de/adhoc/uri/U3RlaW5kbCwgS2F0aGFyaW5h|https://orcid.org/0000-0003-2930-3163|https://frl.publisso.de/adhoc/uri/TXVmZmVscywgSXJlbmE=|https://orcid.org/0000-0001-9821-8398|https://orcid.org/0000-0002-1368-1023|https://orcid.org/0000-0002-0119-5896|https://frl.publisso.de/adhoc/uri/TGUgR3V5YWRlciwgR3dlbmHDq2w=|https://orcid.org/0000-0001-8589-6018|https://orcid.org/0000-0001-8008-9145|https://orcid.org/0000-0003-3717-8374|https://orcid.org/0000-0001-7098-6520|https://orcid.org/0000-0002-2523-1230|https://frl.publisso.de/adhoc/uri/dmFuIFNsZWd0ZW5ob3JzdCwgTWFyam9uIEEu|https://orcid.org/0000-0001-9713-7107|https://orcid.org/0000-0002-9533-7217|https://orcid.org/0000-0001-7941-1774|https://orcid.org/0000-0003-0723-0960|https://orcid.org/0000-0002-1277-5298|https://frl.publisso.de/adhoc/uri/Tm9tdXJhLCBZdW1pa28=|https://orcid.org/0000-0002-6788-1151|https://orcid.org/0000-0002-8644-5507|https://frl.publisso.de/adhoc/uri/RG9ic29uLCBBbXk=|https://frl.publisso.de/adhoc/uri/UGxvbXAsIEFzdHJpZCBTLg==|https://frl.publisso.de/adhoc/uri/TW90YXphY2tlciwgTS4gTWFoZGk=|https://frl.publisso.de/adhoc/uri/S2Fpc2VyLCBGcmFuayBKLg==|https://orcid.org/0000-0002-8926-9692|https://orcid.org/0000-0001-9147-2406|https://orcid.org/0000-0002-7212-9554|https://orcid.org/0000-0002-3462-3463
1000 Hinweis
  • DeepGreen-ID: c2132bb1acd64515be2646f1ae19fa6f ; 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)
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1000 Erstellt am 2023-04-28T14:19:16.025+0200
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1000 Zuletzt bearbeitet Fri Oct 20 19:06:05 CEST 2023
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