Exome sequencing identifies a recurrent SOX2 deletion in a patient with gait ataxia and dystonia lacking major ocular malformations

  • Robin A. Pilz
    Affiliations
    Department of Human Genetics, University Medicine Greifswald, and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Fleischmannstraße 43, 17475 Greifswald, Germany
    Search for articles by this author
  • G. Christoph Korenke
    Affiliations
    Department of Neuropediatrics, University Children's Hospital, Klinikum Oldenburg, Rahel-Straus-Straße 10, 26133 Oldenburg, Germany
    Search for articles by this author
  • Rainer Steeb
    Affiliations
    Opthalmologist, Friedrich-Paffrath-Straße 98, 26389 Wilhelmshaven, Germany
    Search for articles by this author
  • Tim M. Strom
    Affiliations
    Institute of Human Genetics, Technische Universität München, Trogerstraße. 32, 81675 Munich, Germany

    Institute of Human Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany
    Search for articles by this author
  • Ute Felbor
    Affiliations
    Department of Human Genetics, University Medicine Greifswald, and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Fleischmannstraße 43, 17475 Greifswald, Germany
    Search for articles by this author
  • Matthias Rath
    Correspondence
    Corresponding author at: Department of Human Genetics, University Medicine Greifswald, Fleischmannstraße 43, D 17475 Greifswald, Germany.
    Affiliations
    Department of Human Genetics, University Medicine Greifswald, and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Fleischmannstraße 43, 17475 Greifswald, Germany
    Search for articles by this author
Published:April 08, 2019DOI:https://doi.org/10.1016/j.jns.2019.04.007

      Highlights

      • The expressivity of SOX2-related disorders is more variable than previously thought.
      • Eye malformations are common but not obligatory features of SOX2-related disorders.
      • SOX2 mutation carriers may present with ataxia and complex movement disorders.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal

      Subscribe:

      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Dennert N.
        • Engels H.
        • Cremer K.
        • Becker J.
        • Wohlleber E.
        • Albrecht B.
        • et al.
        De novo microdeletions and point mutations affecting SOX2 in three individuals with intellectual disability but without major eye malformations.
        Am. J. Med. Genet. A. 2017; 173: 435-443
        • Blackburn P.R.
        • Chacon-Camacho O.F.
        • Ortiz-Gonzalez X.R.
        • Reyes M.
        • Lopez-Uriarte G.A.
        • Zarei S.
        • et al.
        Extension of the mutational and clinical spectrum of SOX2 related disorders: Description of six new cases and a novel association with suprasellar teratoma.
        Am. J. Med. Genet. A. 2018; 176: 2710-2719
        • Errichiello E.
        • Gorgone C.
        • Giuliano L.
        • Iadarola B.
        • Cosentino E.
        • Rossato M.
        • et al.
        SOX2: Not always eye malformations. Severe genital but no major ocular anomalies in a female patient with the recurrent c.70del20 variant.
        Eur J Med Genet. 2018; 61: 335-340
        • Zenteno J.C.
        • Perez-Cano H.J.
        • Aguinaga M.
        Anophthalmia-esophageal atresia syndrome caused by an SOX2 gene deletion in monozygotic twin brothers with markedly discordant phenotypes.
        Am. J. Med. Genet. A. 2006; 140: 1899-1903
        • Schneider A.
        • Bardakjian T.
        • Reis L.M.
        • Tyler R.C.
        • Semina E.V.
        Novel SOX2 mutations and genotype-phenotype correlation in anophthalmia and microphthalmia.
        Am. J. Med. Genet. A. 2009; 149A: 2706-2715
        • Ragge N.K.
        • Lorenz B.
        • Schneider A.
        • Bushby K.
        • de Sanctis L.
        • de Sanctis U.
        • et al.
        SOX2 anophthalmia syndrome.
        Am. J. Med. Genet. A. 2005; 135: 1-7
        • Zhou J.
        • Kherani F.
        • Bardakjian T.M.
        • Katowitz J.
        • Hughes N.
        • Schimmenti L.A.
        • et al.
        Identification of novel mutations and sequence variants in the SOX2 and CHX10 genes in patients with anophthalmia/microphthalmia.
        Mol. Vis. 2008; 14: 583-592
        • Numakura C.
        • Kitanaka S.
        • Kato M.
        • Ishikawa S.
        • Hamamoto Y.
        • Katsushima Y.
        • et al.
        Supernumerary impacted teeth in a patient with SOX2 anophthalmia syndrome.
        Am. J. Med. Genet. A. 2010; 152A: 2355-2359
        • Schilter K.F.
        • Reis L.M.
        • Schneider A.
        • Bardakjian T.M.
        • Abdul-Rahman O.
        • Kozel B.A.
        • et al.
        Whole-genome copy number variation analysis in anophthalmia and microphthalmia.
        Clin. Genet. 2013; 84: 473-481
        • Cerrato V.
        • Mercurio S.
        • Leto K.
        • Fuca E.
        • Hoxha E.
        • Bottes S.
        • et al.
        Sox2 conditional mutation in mouse causes ataxic symptoms, cerebellar vermis hypoplasia, and postnatal defects of Bergmann glia.
        Glia. 2018; 66: 1929-1946
        • Zhang S.
        • Zhu X.
        • Gui X.
        • Croteau C.
        • Song L.
        • Xu J.
        • et al.
        Sox2 Is Essential for Oligodendroglial Proliferation and Differentiation during Postnatal Brain Myelination and CNS Remyelination.
        J. Neurosci. 2018; 38: 1802-1820