The limb-girdle muscular dystrophies are a group of disorders with wide genetic and clinical heterogeneity. Recently, mutations in the ANO5 gene, which encodes a putative calcium-activated chloride channel belonging to the Anoctamin family of proteins, were identified in five families with one of two previously identified disorders, limb-girdle muscular dystrophy 2L and non-dysferlin Miyoshi muscular dystrophy. We screened a candidate group of 64 patients from 59 British and German kindreds and found the truncating mutation, c.191dupA in exon 5 of ANO5 in 20 patients, homozygously in 15 and in compound heterozygosity with other ANO5 variants in the rest. An intragenic single nucleotide polymorphism and an extragenic microsatellite marker are in linkage disequilibrium with the mutation, suggesting a founder effect in the Northern European population. We have further defined the clinical phenotype of ANO5-associated muscular dystrophy. Patients show adult onset proximal lower limb weakness with highly raised serum creatine kinase values (average 4500 IU/l) and frequent muscle atrophy and asymmetry of muscle involvement. Onset varies from the early 20 s to 50 s and the weakness is generally slowly progressive, with most patients remaining ambulant for several decades. Distal presentation is much less common but a milder degree of distal lower limb weakness is often observed. Upper limb strength is only mildly affected and cardiac and respiratory function is normal. Females appear less frequently affected. In the North of England population we have identified eight patients with ANO5 mutations, suggesting a minimum prevalence of 0.27/100,000, twice as common as dysferlinopathy. We suggest that mutations in ANO5 represent a relatively common cause of adult onset muscular dystrophy with high serum creatine kinase and that mutation screening, particularly of the common mutation c.191dupA, should be an early step in the diagnostic algorithm of adult limb-girdle muscular dystrophy patients.

1 A colonic delivery system is described to deliver orally ingested drugs to the colon and release them at that site by coating with an acrylic based resin (Eudragit S). The technique is validated using X-ray evidence and serum levels of a convenient marker, sulphapyridine.2 This colonic delivery system is particularly suitable for drugs such as 5-amino salicyclic acid or steroids in the management of patients with colitis.

Summary  Neurobiological mechanisms of human musculoskeletal pain are poorly understood. This case‐control study tested the hypothesis that biomarkers within temporomandibular muscle and joint disorders (TMJD) subjects’ masseter muscles or temporomandibular joint (TMJ) synovial fluid correlate with plasma biomarker concentrations. Fifty subjects were recruited and categorized into TMJD cases (n = 23) and pain‐free controls (n = 27) at the University of Minnesota School of Dentistry. Prior to specimen collection, pain intensity and pressure pain threshold masseter muscles and the TMJs were assessed. We collected venous blood; biopsied masseter muscle; and sampled TMJ synovial fluid on the subjects’ side of maximum pain intensity. We assayed these tissues for the presence of nerve growth factor (NGF), bradykinin (BK), leukotreine B4 (LTB4) and prostaglandin E2 (PGE2), F2‐isoprostane (F2I) and substance P (SP). The data was analyzed using Spearman Correlation Coefficients. We found that only plasma concentrations of bradykinin statistically correlated with synovial fluid concentrations (ρ = −0·48, P = 0·005), but no association was found between pain intensities. The data suggests that biomarkers used to assess TMJD need to be acquired in a site‐specific manner. We also discovered that F2I concentrations were associated with muscle pain intensity and muscle pressure pain threshold (PTT) (β = 0·4, 95%CI: 0·03–0·8) and joint PPT (β = 0·4, 95%CI: 0·07–0·8) suggesting that muscle oxidative stress is involved in myofascial pain and that F2‐I may be a biomarker for myofascial pain.

This study has established the range of OSS in the asymptomatic adult population. Symptom scores can only be used effectively when the range in the asymptomatic population is known. This is so that disease severity can be gauged in the context of the normal population and post-operative improvements can be forecast more accurately.

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