Mutations in the HSPB8, or heat shock protein family B (small) member 8, is a member of the chaperone-assisted selective autophagy complex and has recently been associated with rimmed vacuolar myopathy. We report a family with a HSPB8 rimmed vacuolar myopathy caused by a novel c.515delC variant with progressive muscle weakness, pathological findings of rimmed vacuoles of muscle biopsy, and one individual who died of cardiomyopathy. Whole exome sequencing analyses revealed a c.515delC, resulting in a translational frameshift expected to elongate the protein by an additional 49 amino acid tail. We reviewed the clinical characteristics of all reported patients (N= 26, 15 males and 11 females) in the literature, and performed a genotype/phenotype analysis. Males in the families appeared to present with an earlier age of onset, more severe muscle weakness compared to females, and a higher prevalence of other organ system complications including cardiomyopathy in two males. In conclusion, this family expands the phenotype/genotype correlations in HSPB8-associated myopathy with rimmed vacuoles and c.515 delC. We note that c.515 appears to be a hot spot, and the phenotype appears to be more severe in males in this disease, with an earlier onset of the myopathy.

The authors have declared no competing interest.

Inclusion Body Myopathy Foundation.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by the University of California Irvine Institutional Review Board (IRB 2007-5832).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present work are contained in the manuscript