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.