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Congenital Myasthenic Syndrome due to DOK7 mutations in a family from Chile

Jorge A. Bevilacqua, Marian Lara, Jorge Díaz, Mario Campero, Jessica Vászquez, Ricardo A. Maselli
  • Jorge A. Bevilacqua
    Neuromuscular Unit, Department of Neurology and Neurosurgery, University of Chile Clinical Hospital (HCUCH), Santiago; Program of Anatomy and Developmental Biology, Biomedical Sciences Institute (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile | jbevilac@med.uchile.cl
  • Marian Lara
    Department of Neurology, University of California Davis, Davis, CA, United States
  • Jorge Díaz
    Department of Radiology, University of Chile Clinical Hospital (HCUCH), Santiago, Chile
  • Mario Campero
    Neuromuscular Unit, Department of Neurology and Neurosurgery, University of Chile Clinical Hospital (HCUCH), Santiago, Chile
  • Jessica Vászquez
    Department of Neurology, University of California Davis, Davis, CA, United States
  • Ricardo A. Maselli
    Department of Neurology, University of California Davis, Davis, CA, United States

Abstract

Congenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. A 61-year-old female and her older sister showed bilateral ptosis, facial and proximal limb weakness, and scoliosis since childhood. Another female sibling had milder signs, while other family members were asymptomatic. Facial nerve repetitive stimulation in the proband showed decrement of muscle responses. Single fiber EMG revealed increased jitter and blocking. Muscle biopsy showed type 2-fiber atrophy, without tubular aggregates. Mutational analysis in the three affected siblings revealed two compound heterozygous mutations in DOK7: c.1457delC, that predicts p.Pro486Argfs*13 and truncates the protein C-terminal domain, and c.473G>A, that predicts p.Arg158Gln and disruption of the dok7-MuSK interaction in the phosphotyrosine binding (PTB) domain. Unaffected family members carried only one or neither mutation. Discussion. Two of the affected sisters showed marked improvement with salbutamol treatment, which illustrates the benefits of a correct diagnosis and treatment of DOK7-CMS.

Keywords

Myasthenic syndromes, congenital, dok-7, Electrophysiology, salbutamol, MRI

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Submitted: 2017-06-06 22:32:15
Published: 2017-09-20 14:35:46
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Copyright (c) 2017 Jorge A Bevilacqua, Marian Lara, Jorge Díaz, Mario Campero, Jessica Vászquez, Ricardo A. Maselli

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