Publications by authors named "C C Weihl"
Objective: Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP) natural history study.
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- TDP-43 is an RNA binding protein that forms aggregates in the central nervous system and is notably present in certain neurodegenerative diseases and inclusion body myopathy, a type of muscle disease.
- Researchers developed a mouse model that shows muscle weakness associated with TDP-43 accumulation, which indicates a prion-like spread of the protein possibly affecting muscle tissues.
- Human muscle biopsies from patients with various conditions, especially inclusion body myositis (IBM), contain TDP-43 aggregate seeds, suggesting a unique pathogenic role for TDP-43 in muscle diseases that wasn't fully recognized before.
Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood.
View Article and Find Full Text PDFProtein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood.
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- Multisystem proteinopathy-1 (MSP1) is a late-onset genetic disease linked to over 50 mutations in the p97/VCP protein, leading to various symptoms like myopathy, Paget’s disease, and dementia without clear genotype-phenotype relationships.* -
- Research involved analyzing MSP1 patients' data from literature and a registry, focusing on the age of onset and loss of mobility, while also examining the ATPase activity of the VCP protein.* -
- Findings showed that one common variant (R155C) had an earlier onset and higher ATPase activity, highlighting a potential link between VCP activity levels and disease onset, suggesting that regulating this activity could be a new treatment strategy