Fulltext

Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P

Walter, M. C. ; Reilich, P. ; Huebner, A. ; Fischer, D. ; Schröder, R. ; Vorgerd, M. ; Kress, W. ; Born, C. ; Schoser, B. G. ; Krause, K. H. ; Klutzny, U. ; Bulst, S. ; Frey, J. R. ; Lochmüller, H.

In: Brain, 2007, vol. 130, no. 6, p. 1485-1496

Aggiungi alla tua lista
    Titre
    • Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P
    Auteur
    • Walter, M. C.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Reilich, P.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Huebner, A.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Fischer, D.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Schröder, R.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Vorgerd, M.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Kress, W.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Born, C.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Schoser, B. G.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Krause, K. H.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Klutzny, U.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Bulst, S.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Frey, J. R.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    • Lochmüller, H.. Friedrich Baur Institute, Department of Neurology and Institute for Clinical Radiology, Ludwig Maximilians University of Munich, Children's Hospital, Technical University, Dresden, Muscle center and ALS clinic, Kantonspital St Gallen, Switzerland, Center of Biochemistry, University of Cologne, Department of Neurology, Ruhr-University of Bochum, Institute for Human Genetics, University of Würzburg, Germany and Hoffmann-La Roche and CNS Research, Basel, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Brain, 2007, vol. 130, no. 6, p. 1485-1496. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:302878
    Summary
    In 1965, an adult-onset, autosomal dominant disorder with a peculiar scapuloperoneal distribution of weakness and atrophy was described in a large, multi-generation kindred and named ‘scapuloperoneal syndrome type Kaeser' (OMIM #181400). By genetic analysis of the original kindred, we discovered a heterozygous missense mutation of the desmin gene (R350P) cosegregating with the disorder. Moreover, we detected DES R350P in four unrelated German families allowing for genotype-phenotype correlations in a total of 15 patients carrying the same mutation. Large clinical variability was recognized, even within the same family, ranging from scapuloperoneal (n = 2, 12%), limb girdle (n = 10, 60%) and distal phenotypes (n = 3, 18%) with variable cardiac (n = 7, 41%) or respiratory involvement (n = 7, 41%). Facial weakness, dysphagia and gynaecomastia were frequent additional symptoms. Overall and within each family, affected men seemingly bear a higher risk of sudden, cardiac death as compared to affected women. Moreover, histological and immunohistochemical examination of muscle biopsy specimens revealed a wide spectrum of findings ranging from near normal or unspecific pathology to typical, myofibrillar changes with accumulation of desmin. This study reveals that the clinical and pathological variability generally observed in desminopathies may not be attributed to the nature of the DES mutation alone, but may be influenced by additional genetic and epigenetic factors such as gender. In addition, mutations of the desmin gene should be considered early in the diagnostic work-up of any adult-onset, dominant myopathy, even if specific myofibrillar pathology is absent