Advertisement

Correspondence on “Variants in MED12L, encoding a subunit of the mediator kinase module, are responsible for intellectual disability associated with transcriptional defect” by Nizon et al

  • Marina Kossmann Ferraz
    Affiliations
    Medical Genetics Service, Gaffrée and Guinle University Hospital, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

    D’Or Institute of Research and Education (IDOR), Rio de Janeiro, Brazil
    Search for articles by this author
  • Ana Carolina Esposito
    Affiliations
    Medical Genetics Service, Gaffrée and Guinle University Hospital, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
    Search for articles by this author
  • Cláudio Schmidt
    Affiliations
    Centro de Genética Médica do Rio de Janeiro, Rio de Janeiro, Brazil
    Search for articles by this author
  • Maria Angélica Lima
    Affiliations
    Medical Genetics Service, Gaffrée and Guinle University Hospital, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
    Search for articles by this author
  • Fernando Regla Vargas
    Correspondence
    Correspondence and requests for materials should be addressed to Fernando Regla Vargas, Birth Defects Epidemiology Laboratory, Oswaldo Cruz Institute, Fundação Oswaldo Cruz, Room 617, Pav Leônidas Deane, Av Brasil 4365, 21040-360, Rio de Janeiro, RJ, Brazil.
    Affiliations
    Medical Genetics Service, Gaffrée and Guinle University Hospital, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

    Birth Defects Epidemiology Laboratory, Oswaldo Cruz Institute, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
    Search for articles by this author
Published:August 03, 2022DOI:https://doi.org/10.1016/j.gim.2022.05.019
      We read with great interest the article by Nizon et al,

      Nizon M, Laugel V, Flanigan KM, et al. Variants in MED12L, encoding a subunit of the mediator kinase module, are responsible for intellectual disability associated with transcriptional defect. Genet Med. 2019;21(12):2713-2722. Published correction appears in Genet Med. 2019;21(11):2663. https://doi.org/10.1038/s41436-019-0557-3.

      in which the authors have described a cohort of 7 unrelated individuals with intellectual disability/developmental delay and loss-of-function variants in MED12L gene. The phenotype was characterized by intellectual disability/developmental delay (7/7), speech and motor impairment (7/7), seizures (1/7), gastrointestinal anomalies (5/7), facial and hand dysmorphic signs (5/7), and callosal dysgenesis (2/4). All probands had a germline loss-of-function variant in MED12L gene, and the pathogenic variant was de novo in 4 of 4 patients. This condition was named Nizon-Izidor syndrome (OMIM 618872). To the best of our knowledge, no other patients with this condition were published in the literature.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      ACMG Member Login

      Are you an ACMG Member? Sign in for online access.

      Subscribe:

      Subscribe to Genetics in Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. Nizon M, Laugel V, Flanigan KM, et al. Variants in MED12L, encoding a subunit of the mediator kinase module, are responsible for intellectual disability associated with transcriptional defect. Genet Med. 2019;21(12):2713-2722. Published correction appears in Genet Med. 2019;21(11):2663. https://doi.org/10.1038/s41436-019-0557-3.

        • Wan C.
        • Borgeson B.
        • Phanse S.
        • et al.
        Panorama of ancient metazoan macromolecular complexes.
        Nature. 2015; 525: 339-344https://doi.org/10.1038/nature14877
        • Ono T.
        • Fang Y.
        • Spector D.L.
        • Hirano T.
        Spatial and temporal regulation of condensins I and II in mitotic chromosome assembly in human cells.
        Mol Biol Cell. 2004; 15: 3296-3308https://doi.org/10.1091/mbc.e04-03-0242
        • Gerlich D.
        • Hirota T.
        • Koch B.
        • Peters J.M.
        • Ellenberg J.
        Condensin I stabilizes chromosomes mechanically through a dynamic interaction in live cells.
        Curr Biol. 2006; 16: 333-344https://doi.org/10.1016/j.cub.2005.12.040
      2. Martin CA, Murray JE, Carroll P, et al. Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis. Genes Dev. 2016;30(19):2158-2172. Published correction appears in Genes Dev. 2017;31(9):953. https://doi.org/10.1101/gad.286351.116.

        • Green L.C.
        • Kalitsis P.
        • Chang T.M.
        • et al.
        Contrasting roles of condensin I and condensin II in mitotic chromosome formation.
        J Cell Sci. 2012; 125: 1591-1604https://doi.org/10.1242/jcs.097790
        • Zhang S.
        • Übelmesser N.
        • Josipovic N.
        • et al.
        RNA polymerase II is required for spatial chromatin reorganization following exit from mitosis.
        Sci Adv. 2021; 7eabg8205https://doi.org/10.1126/sciadv.abg8205
        • Allen B.L.
        • Taatjes D.J.
        The Mediator complex: a central integrator of transcription.
        Nat Rev Mol Cell Biol. 2015; 16: 155-166https://doi.org/10.1038/nrm3951

      Linked Article

      • Response to Kossmann Ferraz et al
        Genetics in MedicineVol. 24Issue 10
        • Preview
          In their letter, Kossmann Ferraz et al1 reported a patient affected by a neurodevelopmental disorder and carrying a germline de novo loss-of-function variant (c.971del;p.(pro324Glnfs∗18)) in MED12L. This boy also carries 2 de novo chromosomal balanced reciprocal translocations: 46,XY,t(1;2)(p33;p22),t(5;9)(p15;q21). This lead them to ask if a loss-of-function MED12L variant could induce chromosomal instability and be responsible for a de novo rearrangement.
        • Full-Text
        • PDF