Genes and Genomics

The Genetics Society of Korea (한국유전학회)
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BAG3 mutation in a patient with atypical phenotypes of myofibrillar myopathy and Charcot-Marie-Tooth disease

  • Kim, Seung Ju (Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Nam, Soo Hyun (Stem Cell & Regenerative Medicine Institute, Samsung Medical Center) ;
  • Kanwal, Sumaira (Department of Biosciences, COMSATS Institute of Information Technology) ;
  • Nam, Da Eun (Department of Biological Sciences, Kongju National University) ;
  • Yoo, Da Hye (Department of Biological Sciences, Kongju National University) ;
  • Chae, Jong?Hee (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Suh, Yeon?Lim (Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Chung, Ki Wha (Department of Biological Sciences, Kongju National University) ;
  • Choi, Byung?Ok (Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2018.04.04
  • Accepted : 2018.07.18
  • Published : 2018.12.31
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Abstract

Bcl2-associated athanogene 3 (BAG3) mutations have been reported to cause the myofibrillar myopathy (MFM) which shows progressive limb muscle weakness, respiratory failure, and cardiomyopathy. Myopathy patients with BAG3 mutation are very rare. We described a patient showing atypical phenotypes. We aimed to find the genetic cause of Korean patients with sensory motor polyneuropathy, myopathy and rigid spine. We performed whole exome sequencing (WES) with 423 patients with sensory motor polyneuropathy. We found BAG3 mutation in one patient with neuropathy, myopathy and rigid spine syndrome, and performed electrophysiological study, whole body MRI and muscle biopsy on the patient. A de novo heterozygous p.Pro209Leu (c.626C>T) mutation in BAG3 was identified in a female myopathy. She first noticed a gait disturbance and spinal rigidity at the age of 11, and serum creatine kinase levels were elevated ninefolds than normal. She showed an axonal sensory-motor polyneuropathy like Charcot-Marie-Tooth disease (CMT), myopathy, rigid spine and respiratory dysfunction; however, she did not show any cardiomyopathy, which is a common symptom in BAG3 mutation. Lower limb MRI and whole spine MRI showed bilateral symmetric fatty atrophy of muscles at the lower limb and paraspinal muscles. When we track traceable MRI 1 year later, the muscle damage progressed slowly. As far as our knowledge, this is the first Korean patient with BAG3 mutation. We described a BAG3 mutation patient with atypical phenotype of CMT and myopathy, and those are expected to broaden the clinical spectrum of the disease and help to diagnose it.

Keywords

Acknowledgement

Supported by : Ministry of Health & Welfare, National Research Foundation of Korea (NRF)

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