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Gustavson syndrome ...
Gustavson syndrome is caused by an in-frame deletion in RBMX associated with potentially disturbed SH3 domain interactions
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- Johansson, J. (författare)
- Uppsala University
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- Lideus, S. (författare)
- Uppsala University
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- Frykholm, C. (författare)
- Uppsala University
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- Gunnarsson, Cecilia, 1970- (författare)
- Linköping University,Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Klinisk genetik,Region Östergötland, Övr Regionledningskontoret
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- Mihalic, F. (författare)
- Uppsala University
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- Gudmundsson, S. (författare)
- Uppsala University,Broad Institute,Boston Children's Hospital
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- Ekvall, S. (författare)
- Uppsala University
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- Molin, A. M. (författare)
- Uppsala University
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- Pham, M. (författare)
- Uppsala University
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- Vihinen, Mauno (författare)
- Lund University,Lunds universitet,Proteinbioinformatik,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Protein Bioinformatics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Lagerstedt-Robinson, K. (författare)
- Karolinska Institute,Karolinska Institutet,Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden,Karolinska University Hospital
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- Nordgren, Ann, 1964 (författare)
- Karolinska Institute,University of Gothenburg,Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine,Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden; Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden,Sahlgrenska University Hospital,Karolinska University Hospital
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- Jemth, P. (författare)
- Uppsala University
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Ameur, A. (författare)
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- Anneren, G. (författare)
- Uppsala University
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- Wilbe, M. (författare)
- Uppsala University
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- Bondeson, M. L. (författare)
- Uppsala University
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(creator_code:org_t)
- SPRINGERNATURE, 2024
- 2024
- Engelska.
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Ingår i: European Journal of Human Genetics. - : SPRINGERNATURE. - 1018-4813 .- 1476-5438. ; 32:3, s. 333-341
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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http://dx.doi.org/10... (free)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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http://kipublication...
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https://urn.kb.se/re...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- RNA binding motif protein X-linked (RBMX) encodes the heterogeneous nuclear ribonucleoprotein G (hnRNP G) that regulates splicing, sister chromatid cohesion and genome stability. RBMX knock down experiments in various model organisms highlight the gene's importance for brain development. Deletion of the RGG/RG motif in hnRNP G has previously been associated with Shashi syndrome, however involvement of other hnRNP G domains in intellectual disability remain unknown. In the current study, we present the underlying genetic and molecular cause of Gustavson syndrome. Gustavson syndrome was first reported in 1993 in a large Swedish five-generation family presented with profound X-linked intellectual disability and an early death. Extensive genomic analyses of the family revealed hemizygosity for a novel in-frame deletion in RBMX in affected individuals (NM_002139.4; c.484_486del, p.(Pro162del)). Carrier females were asymptomatic and presented with skewed X-chromosome inactivation, indicating silencing of the pathogenic allele. Affected individuals presented minor phenotypic overlap with Shashi syndrome, indicating a different disease-causing mechanism. Investigation of the variant effect in a neuronal cell line (SH-SY5Y) revealed differentially expressed genes enriched for transcription factors involved in RNA polymerase II transcription. Prediction tools and a fluorescence polarization assay imply a novel SH3-binding motif of hnRNP G, and potentially a reduced affinity to SH3 domains caused by the deletion. In conclusion, we present a novel in-frame deletion in RBMX segregating with Gustavson syndrome, leading to disturbed RNA polymerase II transcription, and potentially reduced SH3 binding. The results indicate that disruption of different protein domains affects the severity of RBMX-associated intellectual disabilities.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- rna-binding proteins
- mental-retardation
- crystal-structure
- family
- gene
- sequence
- regions
- expression
- ligand
- sites
- Biochemistry & Molecular Biology
- Genetics & Heredity
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Johansson, J.
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Lideus, S.
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Frykholm, C.
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Gunnarsson, Ceci ...
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Mihalic, F.
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Gudmundsson, S.
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visa fler...
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Ekvall, S.
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Molin, A. M.
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Pham, M.
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Vihinen, Mauno
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Lagerstedt-Robin ...
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Nordgren, Ann, 1 ...
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Jemth, P.
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Ameur, A.
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Anneren, G.
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Wilbe, M.
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Bondeson, M. L.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Medicinsk geneti ...
- Artiklar i publikationen
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European Journal ...
- Av lärosätet
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Göteborgs universitet
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Karolinska Institutet
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Linköpings universitet
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Lunds universitet