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Re-evaluation of the phenotype caused by the common MATR3 p.Ser85Cys mutation in a new family
  1. Johanna Palmio1,
  2. Anni Evilä2,
  3. Ayat Bashir3,
  4. Fiona Norwood4,
  5. Kati Viitaniemi1,
  6. Anna Vihola2,
  7. Sanna Huovinen5,
  8. Volker Straub6,
  9. Peter Hackman2,
  10. Michio Hirano7,
  11. Kate Bushby6,
  12. Bjarne Udd1,2,8
  1. 1 Department of Neurology, Neuromuscular Research Centre, Tampere University and University Hospital, Tampere, Finland
  2. 2 Folkhälsan Institute of Genetics and the Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland
  3. 3 Newcastle University, Newcastle upon Tyne, UK
  4. 4 Department of Neurology, King's College Hospital, London, UK
  5. 5 Department of Pathology, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland
  6. 6 Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, UK
  7. 7 Department of Neurology, Columbia University Medical Centre, New York, New York, USA
  8. 8 Department of Neurology, Vasa Central Hospital, Vasa, Finland
  1. Correspondence to Dr Johanna Palmio, Department of Neurology, Neuromuscular Research Centre, Tampere University and University Hospital, University of Tampere, Tampere 33014, Finland; johanna.palmio{at}uta.fi

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Introduction

Late-onset autosomal dominant vocal cord and pharyngeal distal myopathy (VCPDM) was first described in an American family.1 A p.Ser85Cys mutation in MATR3 gene was later identified in this family, and also in one Bulgarian family and very recently, in seven families—six German and one Asian.2–4 Muscle pathology of VCPDM was dominated by rimmed-vacuolar fibre degeneration.1 ,2 This year, two other mutations in MATR3, p.Phe115Cys and p.Thr622Ala, have been reported to cause autosomal dominant amyotrophic lateral sclerosis (ALS).5 The original American p.Ser85Cys mutated family was re-evaluated and the authors stated: “These clinical findings supported reclassification of this condition as slowly progressive ALS, and the presence of upper motor neuron signs in the form of brisk reflexes ruled out myopathy as the only cause of disease in this family.”5

We report a new family with the p.Ser85Cys mutation in MATR3, in which muscle atrophy and weakness are caused by progressive degenerative myopathy without any evidence of lower motor neuron defects.

Methods

We investigated an American family with four affected siblings. Patients II.1, II.2 and II.4 were more extensively examined and followed for 7, 9 and 8 years, respectively. The father and one of his brothers were affected (figure 1A). Muscle MRI was performed in the proband (II.2) and in the younger brother (II.4). Muscle biopsies were obtained from three patients and examined by standard histochemical and immunohistochemical stainings with antibodies for Matrin 3, TDP-43, p62, SMI-31 and myosin A4.74, slow (MHCs), neonatal (MHCn) and developmental (MHCd) isoforms. Immunofluorescence analysis was performed with conventional methods using antibodies for G3BP and TIA1 C-terminus. Matrin 3 distribution was analysed from soluble cytoplasmic and nuclear fractions using western blotting.

Figure 1

Pedigree and muscle findings of the family. Pedigree of the family (A). Wasting of the first dorsal interossei and thenar …

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