• An international team of doctors and researchers has discovered a new muscle form of chaperonopathy in four patients from three families, two in Spain and one in Saudi Arabia, who had not previously been genetically diagnosed.
• The clinical examination of these patients indicates:
- a manifestation of the disease between the 1st and 4th decade;
- early respiratory failure and vertebral rigidity in all patients;
- axial hypotonia (with Beevor’s sign) and cardiomyopathy observed independently in two patients;
- no developmental delay or limb weakness.
• MRI shows:
- specific involvement of the muscles of the posterior part of the thigh (biceps femoris and semitendinosus), while the anterior part is spared;
- damage to the gluteus maximus muscle in one patient and the calf muscle (soleus) in another.
• The muscle biopsies show:
- atrophied fibres, occasionally angular and more rarely necrotic;
- inclusion bodies and bordered vacuoles.
• Creatine kinase levels range from normal to three times the upper limit of normal.
• Exome sequencing reveals three homozygous mutations in the DNAJB4 gene: one nonsense mutation (c.856A > T; p.Lys286Ter) and two missense mutations (c.74G > A; p.Arg25Gln and c.785 T > C; p.Leu262Ser). The latter two lead to the production of a protein that is either degraded by the cell or stable but non-functional.
• None of the heterozygous mutation carriers were affected by the disease.
