Blog Archives

  In this study, clinical electrophysiology studies, exome and Sanger sequencing were used to identify the molecular basis and elucidate the pathogenesis of a fatal congenital myasthenic syndrome. Clinical electrophysiology studies of the patient revealed several-fold potentiation of the evoked muscle action potential by high frequency nerve stimulation pointing to a presynaptic defect. Exome sequencing … [Read more]

Myotonic dystrophy type 1 (DM1) is caused by (CTG⋅CAG)n-repeat expansion within the DMPK gene and thought to be mediated by a toxic RNA gain of function. Current attempts to develop therapy for this disease mainly aim at destroying or blocking abnormal properties of mutant DMPK (CUG)n RNA. Here, the authors explored a DNA-directed strategy and … [Read more]

  This study describes the phenotypic spectrum of distal hereditary motor neuropathy caused by mutations in the small heat shock proteins HSPB1 and HSPB8 and investigate the functional consequences of newly discovered variants. Among 510 unrelated patients with distal motor neuropathy, the authors identified mutations in HSPB1 (28 index patients/510; 5.5%) and HSPB8 (4 index … [Read more]

The aim of this retrospective study was to evaluate long-term radio-clinical outcome in scapulothoracic fusion using the Letournel technique (where the fourth rib is passed through the wing of the scapula and cerclage wires are tightened to the two ribs below) for patients suffering from facioscapulohumeral muscular dystrophy (FSHMD. Mean improvement in range of motion … [Read more]

There is considerable inter-patient variability in disease onset and progression in Duchenne muscular dystrophy (DMD), which can confound the results of clinical trials. Here the authors show that a common null polymorphism (R577X) in ACTN3 results in significantly reduced muscle strength and a longer 10 m walk test time in young, ambulant patients with DMD; both … [Read more]

Duchenne muscular dystrophy is a rare genetic disorder with life-limiting pathology. Drisapersen induces exon 51 skipping, thereby producing a shorter but functional dystrophin protein. The longest available data are from an open-label extension study (PRO051-02) treating 12 boys with drisapersen (6 mg/kg/week subcutaneously). The median change (range) from baseline to week 177 in six-minute walking … [Read more]

This study aimed to investigate pan-ethnic SMN1 copy-number and sequence variation by hybridization-based target enrichment coupled with massively parallel sequencing or next-generation sequencing (NGS). Ten single-nucleotide variants in SMN1 were detectable by NGS and confirmed by gene-specific amplicon-based sequencing. This comprehensive approach yielded SMA carrier detection rates of 90.3-95.0% in five ethnic groups studied. The … [Read more]

Homozygous SMN1 loss causes spinal muscular atrophy (SMA), the most common lethal genetic childhood motor neuron disease. SMN1 encodes SMN, a ubiquitous housekeeping protein, which makes the primarily motor neuron-specific phenotype rather unexpected. SMA-affected individuals harbor low SMN expression from one to six SMN2 copies, which is insufficient to functionally compensate for SMN1 loss. However, … [Read more]