Phenotype–genotype correlations in patients with Marinesco–Sjögren syndrome

Authors

  • F. Ezgu,

    1. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
    2. Department of Pediatric Metabolic Disorders and Pediatric Genetics, Gazi University Faculty of Medicine, Ankara, Turkey
    Search for more papers by this author
  • P. Krejci,

    1. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
    2. Institute of Experimental Biology, Masaryk University, Brno, Czech Republic
    3. Department of Cytokinetics, Institute of Biophysics ASCR, Brno, Czech Republic
    4. Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA
    Search for more papers by this author
  • S. Li,

    1. Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
    Search for more papers by this author
  • C. de Sousa,

    1. Department of Pediatric Neurology, Great Ormond Street Hospital for Children, London, UK
    Search for more papers by this author
  • J.M. Graham Jr,

    1. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
    2. Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA
    Search for more papers by this author
  • I. Hansmann,

    1. Institut für Humangenetik und Medizinische Biologie, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany
    Search for more papers by this author
  • W. He,

    1. Department of Pathology, M.D.Anderson Cancer Center, Houston, TX, USA
    Search for more papers by this author
  • K. Porpora,

    1. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
    Search for more papers by this author
  • D. Wand,

    1. Institut für Humangenetik und Medizinische Biologie, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany
    Search for more papers by this author
  • W. Wertelecki,

    1. Department of Medical Genetics, University of South Alabama, Mobile, AL, USA
    Search for more papers by this author
  • A. Schneider,

    1. Department of Genetics, Albert Einstein Medical Center, Philadelphia, PA, USA
    Search for more papers by this author
  • W.R. Wilcox

    Corresponding author
    1. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
    2. Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA
    • Corresponding author: William R. Wilcox, MD, PhD, Medical Genetics Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.

      Tel.: +1 310 423 6673;

      fax: +1 310 423 0620;

      e-mail: william.wilcox@cshs.org

    Search for more papers by this author

  • The authors do not declare any conflict of interest.

Abstract

Marinesco–Sjögren syndrome (MSS; MIM 248800) is an autosomal recessive disorder characterized by congenital cerebellar ataxia, early cataracts, developmental delay, myopathy and short stature. Alterations in the gene SIL1 cause MSS in some patients with typical findings. In this study, molecular investigations including sequencing of the SIL1 gene, western blotting and microscopic investigations in fibroblast cultures were carried out in a cohort of 15 patients from 14 unrelated families, including the large, inbred family reported by Superneau et al., having the clinical features of MSS to provide insights into the pathophysiology of the disorder. A total of seven different mutations were found in eight of the patients from seven families. The mutations caused loss of the BIP-associated protein (BAP) protein in four patients by western blot. Novel clinical features such as dental abnormalities, iris coloboma, eczema and hormonal abnormalities were noticed in some patients, but there was no clear way to distinguish those with and without SIL1 mutations. Cultured fibroblasts contained numerous cytoplasmic inclusion bodies, similar to those identified in the brain of the whoozy mouse in five unrelated patients, three with and two without SIL1 mutations, suggesting some SIL1 negative patients share a common cellular pathogenesis with those who are SIL1 positive.

Ancillary