A mutation in HSPB8 leads to axial and proximal myofibrillar myopathy beginning in childhood

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While mutations in HSPB8 have been associated with distal hereditary motor neuropathy (dHMN2A) or Charcot-Marie-Tooth disease type 2L, five variants (including four affecting the last exon) of this gene have been linked to a distal form of myopathy beginning in adulthood. A Chinese team reports a first case of an 18-year-old girl with :

  • a proximal deficit of the lower limbs which began around the age of 6 and progressively worsened,
  • dorsolumbar scoliosis, spinal stiffness and retraction of the neck flexors;
  • a vital capacity of 62% of theoretical;
  • a muscle biopsy revealing classic myofibrillar myopathy.

Whole genome sequencing revealed a de novo mutation shifting the reading frame in the last exon of the HSPB8 gene, resulting in abnormal elongation of the mutated protein, which favours its propensity to form aggregates.

 

Expanding the spectrum of HSPB8-related myopathy: a novel mutation causing atypical pediatric-onset axial and limb-girdle involvement with autophagy abnormalities and molecular dynamics studies. Yang G, Lv X, Yang M et al. J Hum Genet. 2024 Nov 15.

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