Blog Archives
Link between clinical signs of FSHD and DNA methylation
In facioscapulohumeral dystrophy (FSHD), hypomethylation is moderate and heterogeneous in patients. To date, a correlation between hypomethylation and disease presence or severity has not been demonstrated. Here, the authors investigated the link between DNA hypomethylation and clinical penetrance in 95 FSHD cases (37 FSHD1, 29 asymptomatic individuals carrying a shortened D4Z4 array, 9 patients with … [Read more]
Ataluren receives conditional approval in Europe for DMD
The investigational oral drug ataluren, in development to treat Duchenne muscular dystrophy (DMD) resulting from a specific type of genetic mutation, has received conditional approval in the European Union (EU). This designation allows patients to gain access to an experimental drug before it is fully approved. Ataluren, originally known as PTC124 and now bearing the … [Read more]
Ataluren: a promising therapy for patients with nonsense mutation dystrophinopathy
Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. In this randomized, double-blind, placebo-controlled study males ≥5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 … [Read more]
Sildenafil does not improve skeletal and cardiac muscle function in Duchenne/Becker muscular dystrophy
Duchenne and Becker muscular dystrophy (DBMD) are allelic disorders caused by mutations in dystrophin. Patients with DBMB lack neuronal nitric oxide synthase (nNOS), which mediates physiological sympatholysis, thus ensuring adequate blood supply to working muscle. In mice lacking dystrophin, restoration of nNOS effects by a phosphodiesterase 5 (PDE5) inhibitor (sildenafil), improves skeletal and cardiac muscle … [Read more]
Study of brain microstructure in boys with Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness caused by DMD gene mutations leading to absence of the full-length dystrophin protein in muscle. Multiple dystrophin isoforms are expressed in brain, but little is known about their function. DMD is associated with specific learning and behavioral disabilities that are more prominent in patients with … [Read more]
Challenges in management of DMD in Mexico
Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding results in developed nations. This study aimed to describe the status of diagnosis and management of DMD in a developing country through the experience of non-profit organizations. A multistate, multiple-source, population-based survey was performed from medical records of 432 patients. Data were retrospectively collected, reviewed … [Read more]
Systemic FKRP gene delivery in a LGMD2I mouse model
Mutations in fukutin-related protein (FKRP) gene cause a wide spectrum of disease phenotypes including the common limb-girdle muscular dystrophy 2I (LGMD2I), the severe Walker-Warburg syndrome, and muscle-eye-brain disease. FKRP deficiency results in α-dystroglycan (α-DG) hypoglycosylation in the muscle and heart, which is a biochemical hallmark of dystroglycanopathies. To study gene replacement therapy, the authors generated … [Read more]
Congenital muscular dystrophy caused by HRAS mutation
This study reports on a 5-year-old girl who presented with an association of symptoms reminiscent of an Ullrich-like congenital muscular dystrophy including congenital hypotonia, proximal joint contractures, hyperlaxity of distal joints, normal cognitive development, and kyphoscoliosis. There was an excess of neuromuscular spindles on the skeletal muscle biopsy. This very peculiar feature on muscle biopsy … [Read more]
Use of exome sequencing to analyse genes implicated in LGMD or distal myopathies
Autosomal recessive muscular dystrophies are heterogeneous genetic disorders. To date, 39 genes are implicated. Genetic diagnosis using targeted single-gene analysis by Sanger sequencing yields negative results in 10-20% of samples, warranting clinical re-evaluation and time-consuming testing of additional genes. This applies to dysferlinopathies caused by mutations in the gene encoding dysferlin (DYSF), which presents mainly … [Read more]
Early onset and novel features in a spinal and bulbar muscular atrophy patient with a 68 CAG repeat
Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease caused by a trinucleotide (CAG) repeat expansion in the androgen receptor gene. Patients with SBMA have weakness, atrophy, and fasciculations in the bulbar and extremity muscles. Individuals with CAG repeat lengths greater than 62 have not previously been reported. Here, the authors evaluated a … [Read more]
