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1000 Titel
  • De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females
1000 Autor/in
  1. Palmer, E.E. |
  2. Stuhlmann, T. |
  3. Weinert, S. |
  4. Haan, E. |
  5. Van Esch, H. |
  6. Holvoet, M. |
  7. Boyle, J. |
  8. Leffler, M. |
  9. Raynaud, M. |
  10. Moraine, C. |
  11. van Bokhoven, H. |
  12. Kleefstra, T. |
  13. Kahrizi, K. |
  14. Najmabadi, H. |
  15. Ropers, H.-H. |
  16. Delgado, M.R. |
  17. Sirsi, D. |
  18. Golla, S. |
  19. Sommer, A. |
  20. Pietryga, M.P. |
  21. Chung, W.K. |
  22. Wynn, J. |
  23. Rohena, L. |
  24. Bernardo, E. |
  25. Hamlin, D. |
  26. Faux, B.M. |
  27. Grange, D.K. |
  28. Manwaring, L. |
  29. Tolmie, J. |
  30. Joss, S. |
  31. Study, D.D.D. |
  32. Cobben, J.M. |
  33. Duijkers, F.A.M. |
  34. Goehringer, J.M. |
  35. Challman, T.D. |
  36. Hennig, F. |
  37. Fischer, U. |
  38. Grimme, A. |
  39. Suckow, V. |
  40. Musante, L. |
  41. Nicholi, J. |
  42. Shaw, M. |
  43. Lodh, S.P. |
  44. Niu, Z. |
  45. Rosenfeld, J.A. |
  46. Stankiewicz, P. |
  47. Jentsch, T. J. |
  48. Gecz, J. |
  49. Field, M. |
  50. Kalscheuer, V.M. |
1000 Erscheinungsjahr 2016
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2016-08-23
1000 Erschienen in
1000 Quellenangabe
  • Advance online publication
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2016
1000 Lizenz
1000 Verlagsversion
  • http://dx.doi.org/10.1038/mp.2016.135 |
1000 Ergänzendes Material
  • http://www.nature.com/mp/journal/vaop/ncurrent/extref/mp2016135x1.doc |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed in brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females and 2 affected males with a de novo variant in CLCN4 (6 individuals previously unreported) and 27 affected males, 3 affected females and 15 asymptomatic female carriers from 9 families with inherited CLCN4 variants (4 families previously unreported). Intellectual disability ranged from borderline to profound. Behavioral and psychiatric disorders were common in both child- and adulthood, and included autistic features, mood disorders, obsessive–compulsive behaviors and hetero- and autoaggression. Epilepsy was common, with severity ranging from epileptic encephalopathy to well-controlled seizures. Several affected individuals showed white matter changes on cerebral neuroimaging and progressive neurological symptoms, including movement disorders and spasticity. Heterozygous females can be as severely affected as males. The variability of symptoms in females is not correlated with the X inactivation pattern studied in their blood. The mutation spectrum includes frameshift, missense and splice site variants and one single-exon deletion. All missense variants were predicted to affect CLCN4’s function based on in silico tools and either segregated with the phenotype in the family or were de novo. Pathogenicity of all previously unreported missense variants was further supported by electrophysiological studies in Xenopus laevis oocytes. We compare CLCN4-related disorder with conditions related to dysfunction of other members of the CLC family.
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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1000 Label
1000 Förderer
  1. German Ministry of Education and Research |
  2. MRNET |
  3. EU |
  4. Deutsche Forschungsgemeinschaft |
  5. NHMRC |
  6. Simons Foundation |
  7. National Institute of Health |
  8. Columbia University’s Clinical and Translational Science Award (CTSA) |
  9. Health Innovation Challenge Fund |
  10. Wellcome Trust |
  11. Department of Health |
  12. Wellcome Trust Sanger Institute |
1000 Fördernummer
  1. -
  2. -
  3. 241995
  4. SFB740
  5. 628952, 1041920
  6. -
  7. HD057036
  8. UL1 RR024156
  9. HICF-1009-003
  10. -
  11. -
  12. WT098051
1000 Förderprogramm
  1. -
  2. -
  3. FP7 project GENCODYS
  4. -
  5. -
  6. -
  7. -
  8. -
  9. -
  10. -
  11. -
  12. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer German Ministry of Education and Research |
    1000 Förderprogramm -
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer MRNET |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer EU |
    1000 Förderprogramm FP7 project GENCODYS
    1000 Fördernummer 241995
  4. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer SFB740
  5. 1000 joinedFunding-child
    1000 Förderer NHMRC |
    1000 Förderprogramm -
    1000 Fördernummer 628952, 1041920
  6. 1000 joinedFunding-child
    1000 Förderer Simons Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  7. 1000 joinedFunding-child
    1000 Förderer National Institute of Health |
    1000 Förderprogramm -
    1000 Fördernummer HD057036
  8. 1000 joinedFunding-child
    1000 Förderer Columbia University’s Clinical and Translational Science Award (CTSA) |
    1000 Förderprogramm -
    1000 Fördernummer UL1 RR024156
  9. 1000 joinedFunding-child
    1000 Förderer Health Innovation Challenge Fund |
    1000 Förderprogramm -
    1000 Fördernummer HICF-1009-003
  10. 1000 joinedFunding-child
    1000 Förderer Wellcome Trust |
    1000 Förderprogramm -
    1000 Fördernummer -
  11. 1000 joinedFunding-child
    1000 Förderer Department of Health |
    1000 Förderprogramm -
    1000 Fördernummer -
  12. 1000 joinedFunding-child
    1000 Förderer Wellcome Trust Sanger Institute |
    1000 Förderprogramm -
    1000 Fördernummer WT098051
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6403602.rdf
1000 Erstellt am 2017-07-27T15:09:08.243+0200
1000 Erstellt von 22
1000 beschreibt frl:6403602
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet 2022-10-21T18:23:05.753+0200
1000 Objekt bearb. Fri Oct 21 18:23:05 CEST 2022
1000 Vgl. frl:6403602
1000 Oai Id
  1. oai:frl.publisso.de:frl:6403602 |
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