EP 9: Journal Club, Yang et al, 2024 | New Insights Into Pediatric Case of MFM13

EP 11: Living with MFM13: Stories Behind the Diagnosis

In this episode, we focus on the patient journey in MFM13, sharing real-life stories from individuals affected by HSPB8-related myopathy. Through their experiences, we explore the challenges of early symptoms, delayed diagnosis, disease progression, and the impact on daily life and families. We also one more time introduce CureMFM13, a patient-driven initiative dedicated to accelerating research, building a strong community, and working toward effective treatments and a cure. This episode is ideal for patients, families, clinicians, and researchers interested in MFM13, rare neuromuscular diseases, and the real-world impact of living with a progressive myopathy.

EP 10: Journal Club: Inoue and Weihl, 2025 | What Makes an MFM? Rethinking Disease Mechanisms

This podcast discusses the recent publication by Inoue and Weihl (2025) on myofibrillar myopathies (MFMs), focusing on their redefinition as “Z-disk-opathies.” In this episode we explore how new genetic findings challenge the traditional, histopathology-based classification and highlight key disease mechanisms, including Z-disk disruption and impaired protein homeostasis. The episode also covers the distinction between so called, true MFMs and other myopathies with similar pathology, as well as the implications for diagnosis and future targeted therapies.

EP 9: Journal Club, Yang et al, 2024 | New Insights Into Pediatric Case of MFM13

In this Journal Club episode, we review the publication by Yang et al., 2024, which presents the first Chinese case of Myofibrillar Myopathy type 13 with Rimmed Vacuoles (MFM13) in a pediatric patient. Unlike previously reported MFM13 cases, this young patient exhibits axial and limb-girdle muscle involvement, highlighting a novel early-onset presentation. This episode is ideal for researchers, clinicians, and patients interested in MFM13, HSPB8 myopathy, rare pediatric neuromuscular cases, and autophagy-related mechanisms. Please note that the article refers to the MFM13 disease as HSPB8-related myopathy.

EP 8: Clinical features of HSPB8 myopathy

In this episode, we summarize what is known about Myofibrillar Myopathy type 13 (MFM13), previously referred to as HSPB8 Myopathy. Drawing on nine published case studies, we outline the main clinical features — progressive muscle weakness and atrophy, usually starting in the distal lower limbs and leading to foot drop and steppage gait. In some cases, weakness extends to proximal and axial muscles, occasionally affecting breathing or cardiac function. We also discuss the characteristic pathological findings seen in muscle biopsies: rimmed vacuoles, myofibrillar disorganization, and accumulation of proteins like HSPB8, BAG3, and TDP-43. MRI scans often reveal selective fatty degeneration of paraspinal and leg muscles. Finally, we highlight the key discovery that frameshift mutations in HSPB8 result in an abnormal C-terminal peptide extension, creating a toxic gain-of-function mechanism that disrupts autophagy and cellular proteostasis — defining the molecular basis of MFM13. Learn more about our work at curemfm13.org [http://curemfm13.org], and follow us on Facebook, LinkedIn, X, and Bluesky — just search for CureMFM13.

EP 7: Tedesco et al. 2025: How New Frameshifts Change HSPB8 Disease

In this episode, we look at the 2025 study by Tedesco et al., “Novel HSPB8 mutations in severe early-onset myopathy with involvement of respiratory and cardiac muscles cause proteostasis defects in cell models,” published in the European Journal of Human Genetics. The researchers revealed three new mutations in HSPB8 that result in a previously undescribed frameshift. These mutations create a longer C-terminal end of the protein with a different amino acid sequence than those described before. This structural change is linked to an even more severe disease picture: earlier muscle weakness, sometimes combined with reduced involvement, breathing difficulties, and even cardiac problems. The study not only presents detailed case reports but also builds on Tedesco et al., 2023 (Episode 5), which showed how elongated C-terminal mutations disrupt the cell’s clean-up system. In the 2025 work, scientists demonstrate that these new frameshifts also cause toxic aggregation of CASA complex proteins, further impairing the cell’s ability to remove damaged proteins. These results highlight the vulnerability of the HSPB8 gene’s last exon and broaden both the molecular and clinical understanding of HSPB8-related myopathies and neuromyopathies