Blog Archives
Recessive mutations in the kinase ZAK cause a congenital myopathy with fibre type disproportion
Congenital myopathies define a heterogeneous group of neuromuscular diseases with neonatal or childhood hypotonia and muscle weakness. The genetic cause is still unknown in many patients, precluding genetic counselling and better understanding of the physiopathology. To identify novel genetic causes of congenital myopathies, exome sequencing was performed in three consanguineous families. Two homozygous frameshift … [Read more]
Exposure to Myozyme in LOPD patients results in early development of antibodies to the protein which decrease with continued ERT
Immunogenicity of recombinant human acid-alpha glucosidase (rhGAA) in enzyme replacement therapy (ERT) is a safety and efficacy concern in the management of late-onset Pompe disease (LOPD). However, long-term effects of ERT on humoral and cellular responses to rhGAA are still poorly understood. To better understand the impact of immunogenicity of rhGAA on the efficacy … [Read more]
Receptor tyrosine kinase inhibitors: a potential therapeutic strategy for FSHD?
Facioscapulohumeral muscular dystrophy (FSHD) involves sporadic expression of DUX4, which inhibits myogenesis and is pro-apoptotic. To identify target genes, the authors over-expressed DUX4 in myoblasts and found that the receptor tyrosine kinase (RTK) Ret was significantly up-regulated, suggesting a role in FSHD. They demonstrate that Ret is a novel mediator of satellite cell function, … [Read more]
Potential of anisotropic alterations as novel indices of disease status
In this study, the authors sought to understand the alteration in the anisotropic, or direction dependent, character of muscle as measured by electrical impedance myography (EIM) in 36 boys with DMD (27 healthy controls) and its potential to serve as a biomarker of disease status. Normalised reactance anisotropy, a direction-dependent measure of membrane charge … [Read more]
Identification of a novel form of muscular dystrophy with reduced Notch signaling and satellite cell loss
Skeletal muscle regeneration by muscle satellite cells is a physiological mechanism activated upon muscle damage and regulated by Notch signaling. In a family with autosomal recessive limb-girdle muscular dystrophy, the authors identified a missense mutation in POGLUT1 (protein O-glucosyltransferase 1), an enzyme involved in Notch posttranslational modification and function. In vitro and in vivo … [Read more]
Economic evaluation of treatments for DMD
This study aimed to develop a cost-effectiveness model based on the Duchenne muscular dystrophy Functional Ability Self-Assessment Tool (DMDSAT), a new rating scale created specifically to measure disease progression in clinical practice and trials and model DMD in economic evaluations, and compare it with two alternative model structures. Three Markov cohort state-transition models were … [Read more]
Utility of a mixed methods study to identify efficacy of salbutamol in patients with SMA
This longitudinal mixed methods study evaluated the perceived efficacy of salbutamol in adult patients with spinal muscular atrophy (SMA) and the usefulness of the World Health Organization Disability Assessment Schedule II (WHODAS II) and Fatigue Severity Scale (FSS) for its measurement. Ten patients were interviewed and completed WHODAS II and FSS questionnaires to assess … [Read more]
The Italian LGMD registry
The molecular definition of limb girdle muscular dystrophies (LGMDs) is fundamental for prognostic and therapeutic purposes. Here, the authors have created an Italian LGMD registry that includes 370 molecularly defined patients. Detailed retrospective and prospective data were reviewed and each LGMD subtype was compared for differential diagnosis purposes. They found that LGMD types 2A and … [Read more]
Willingness to pay for a newborn screening for SMA
This online willingness-to-pay survey of US adults (n = 982) was conducted to assess population preferences for newborn screening for spinal muscular atrophy (SMA), and how test preferences varied depending on immediate treatment implications. Respondents were asked to imagine being parents of a newborn. Each respondent was presented with two hypothetical scenarios following the … [Read more]
Identification of new TTN mutations causing recessive distal titinopathy
Tibial muscular dystrophy (TMD), the first described human titinopathy, is a mild adult-onset slowly progressive myopathy causing weakness and atrophy in the anterior lower leg muscles. TMD is caused by mutations in the last two exons, Mex5 and Mex6, of the titin gene (TTN). The first reported TMD mutations were dominant, but the Finnish founder … [Read more]
