Opis

• Tytuł:
  The power of the Mediator complex-Expanding the genetic architecture and phenotypic spectrum of MED12 -related disorders
• Twórca:
  Charzewska, Agnieszka;
  Maiwald, R.;
  Kahrizi, K.;
  Oehl-Jaschkowitz, B.;
  Dufke, A.;
  Lemke, J.R.;
  Enders, H.;
  Najmabadi, H.;
  Tzschach, A.;
  Hachmann, W.;
  Jensen, C.;
  Bienek, M.;
  Poznański, Jarosław;
  Nawara, Magdalena;
  Chilarska, T.;
  Obersztyn, Ewa;
  Hoffman-Zacharska, Dorota;
  Gos, Monika;
  Bal, Jerzy;
  Kalscheuer, V.M.
• Opis:
  MED12 is a member of the large Mediator complex that controls cell growth, development, and differentiation. Mutations in MED12 disrupt neuronal gene expression and lead to at least three distinct X-linked intellectual disability (XLID) syndromes (FG, Lujan-Fryns, and Ohdo). Here we describe six families with missense variants in MED12 (p.(Arg815Gln), p.(Val954Gly), p.(Glu1091Lys),p.(Arg1295Cys), p.(Pro1371Ser) and p.(Arg1148His), the latter being firstly reported in affected females) associated with a continuum of symptoms rather than distinct syndromes. The variants expanded the genetic architecture and phenotypic spectrum of MED12-related disorders. New clinical symptoms included brachycephaly, anteverted nares, bulbous nasal tip, prognathism, deep set eyes, and single palmar crease. We showed that MED12 variants, initially implicated in X-linked recessive disorders in males, may predict a potential risk for phenotypic expression in females, with no correlation of the X chromosome inactivation pattern in blood cells. Molecular modeling (Yasara Structure) performed to model the functional effects of the variants strongly supported the pathogenic character of the variants examined. We demonstrated that molecular modeling is a useful method for in silico testing of potential functional effects of MED12 variants and thus can be a valuable addition to the interpretation of the clinical and genetic findings.
• Dostępność obiektu:
  Dostęp otwarty
• Data:
  2018.08
• Typ:
  Article;
  PeerReviewed
• Język:
  angielski
• Format:
  application/pdf
• Wydawca:
  Wiley
• Relacja: http://eprints.ibb.waw.pl/1603 ;http://doi.org/10.1111/cge.13412 ;doi:10.1111/cge.13412
• Temat i słowa kluczowe:
  R Medicine (General)
• Identyfikator: http://eprints.ibb.waw.pl/1603/1/jp2018_Charzewska_et_al-2018-Clinical_Genetics.pdf ;
  Charzewska, Agnieszka and Maiwald, R. and Kahrizi, K. and Oehl-Jaschkowitz, B. and Dufke, A. and Lemke, J.R. and Enders, H. and Najmabadi, H. and Tzschach, A. and Hachmann, W. and Jensen, C. and Bienek, M. and Poznański, Jarosław and Nawara, Magdalena and Chilarska, T. and Obersztyn, Ewa and Hoffman-Zacharska, Dorota and Gos, Monika and Bal, Jerzy and Kalscheuer, V.M. (2018) The power of the Mediator complex-Expanding the genetic architecture and phenotypic spectrum of MED12 -related disorders. Clinical Genetics, 94 (5). pp. 450-456. ISSN 00099163
• Dostawca danych:
  Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk
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