2. Academic Validation
  3. Molecular-genetic characterization and rescue of a TSFM mutation causing childhood-onset ataxia and nonobstructive cardiomyopathy

Molecular-genetic characterization and rescue of a TSFM mutation causing childhood-onset ataxia and nonobstructive cardiomyopathy

  • Eur J Hum Genet. 2016 Jan;25(1):153-156. doi: 10.1038/ejhg.2016.124.
Sonia Emperador 1 2 3,  M Pilar Bayona-Bafaluy 1 3,  Ana Fernández-Marmiesse 2 4,  Mercedes Pineda 2 5,  Blanca Felgueroso 6,  Ester López-Gallardo 1 2 3,  Rafael Artuch 2 5,  Iria Roca 4,  Eduardo Ruiz-Pesini 1 2 3 7,  María Luz Couce 2 4,  Julio Montoya 8 9 10
Affiliations

Affiliations

  • 1 Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain.
  • 2 Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
  • 3 Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Universidad de Zaragoza, Zaragoza, Spain.
  • 4 Departamento de Pediatría, Hospital Clínico Universitario de Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
  • 5 Departamento de Neuropediatría, Hospital San Joan de Deu, Institut de Recerca Pediàtrica (IRP-HSJD), Barcelona, Spain.
  • 6 Departamento de Neurología Pediátrica, Hospital Materno Infantil Teresa Herrera, A Coruña, Spain.
  • 7 Fundación ARAID, Universidad de Zaragoza, Zaragoza, Spain.
  • 8 Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain. [email protected].
  • 9 Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Madrid, Spain. [email protected].
  • 10 Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Universidad de Zaragoza, Zaragoza, Spain. [email protected].
PMID: 27677415 DOI: 10.1038/ejhg.2016.124
Abstract

Oxidative phosphorylation dysfunction has been found in many different disorders. This biochemical pathway depends on mitochondrial protein synthesis. Thus, mutations in components of the mitochondrial translation system can be responsible for some of these pathologies. We identified a new homozygous missense mutation in the mitochondrial translation elongation factor Ts gene in a patient suffering from slowly progressive childhood ataxia and hypertrophic cardiomyopathy. Using cell, biochemical and molecular-genetic protocols, we confirm it as the etiologic factor of this phenotype. Moreover, as an important functional confirmation, we rescued the normal molecular phenotype by expression of the wild-type TSFM cDNA in patient's fibroblasts. Different TSFM mutations can produce the same or very different clinical phenotypes, going from abortions to moderately severe presentations. On the other hand, the same TSFM mutation can also produce same or different phenotypes within the same range of presentations, therefore suggesting the involvement of unknown factors.

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