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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The child that is slow to walk causes concern. When cerebral palsy, mental retardation and muscular dystrophy have been excluded, what remains? Thirty five children (19 boys and 16 girls) with hypermobile joints, blue sclera and bat ears (the 'lax ligament syndrome') were referred by general practitioners to a general paediatric outpatient clinic over two years. Three were referred in the first three months of life because of clicking hips; 14 children aged one to two years, had delayed milestones of motor development and exhibited bottom shuffling; 10 children aged four to five years presented with 'growing pains' or 'funny gait' and eight older children had multiple minor complaints. The lax ligament syndrome is a comparatively common mild collagenopathy. It may well come to light on routine surveillance in general practice. It is dominantly inherited and improves with time; management is therefore expectant and symptomatic. A firm and reassuring diagnosis can be given which saves both anxiety and investigations.
Br J Gen Pract 1990 Jun
PMID:Lax ligament syndrome in children associated with blue sclera and bat ears. 211 44

1. Specific therapies to cure the muscular dystrophies are not yet available. Therapeutic trials designed on the basis of our understanding of the pathophysiology of these disorders have had only limited success. 2. However, recent investigations in Duchenne muscular dystrophy have identified the abnormal gene and the missing or defective gene product, dystrophin. 3. These discoveries provide information which will lead to more rational and specific therapeutic approaches. 4. The advances in genetic research have led to more effective preventive therapy. Gene mapping has been applied successfully in carrier detection and antenatal diagnosis, and specific gene probes will soon become available for carrier testing for the two most common forms of muscular dystrophy, Duchenne muscular dystrophy and myotonic dystrophy. 5. Supportive therapies for muscular dystrophy patients now include respiratory support for selected patients with chronic respiratory insufficiency. 6. This review will focus on the two most common muscular dystrophies, Duchenne muscular dystrophy and myotonic dystrophy.
Gen Pharmacol 1989
PMID:Treatment of muscular dystrophies. 266 27

Dystrophin serves as a link between the subsarcolemmal cytoskeleton and the extracellular matrix. The NH2 terminus attaches to the cytoskeleton, while the COOH terminus attaches to the dystrophin associated protein (DAP) complex, which can be separated into the dystroglycan, sarcoglycan, and syntrophin subcomplexes. While the function of each DAP is not known, the dystroglycan complex binds laminin in the extracellular matrix, and binds the dystrophin COOH terminus in vitro. The syntrophins also bind the dystrophin COOH terminus in vitro, but no evidence has been reported for an interaction between dystrophin and the sarcoglycans. Human mutations have been found in dystrophin, the sarcoglycans and laminin, all of which lead to various types of muscular dystrophy. We have been studying the dystrophin domains necessary for formation of a functional complex by generating transgenic mdx (dystrophin minus) mice expressing internally truncated dystrophins. These mice provide in vivo models to study the localization of truncated dystrophin isoforms, the association of the truncated proteins with the DAP complex, and the functional capacity of the assembled DAP complexes. Expression of a dystrophin deleted for most of the NH2-terminal domain in mdx mice leads to only a mild dystrophy, indicating that dystrophin can attach to the cytoskeleton by multiple mechanisms. Truncation of the central rod domain leads to normal DAP complex formation and almost fully prevents development of dystrophy. Deletion analysis of the COOH-terminal regions indicates that a broad cysteine-rich domain is indispensable for dystrophin function. This region coincides with the in vitro identified beta-dystroglycan binding domain. Mice lacking this latter domain express very low levels of the sarcoglycans, indicating that the sarcoglycan complex binds dystrophin via dystroglycan. All deletion constructs tested lead to normal expression of the syntrophins, indicating that syntrophin associates with the DAP complex via multiple binding partners.
Soc Gen Physiol Ser 1997
PMID:Interactions between dystrophin and the sarcolemma membrane. 921 Feb 17

Myotonic dystrophy type 1 (DM1), the most common form of muscular dystrophy in adults, results from the expression of toxic gain-of-function transcripts containing expanded CUG-repeats. DM1 patients experience cardiac electrophysiological defects, including prolonged PR-, QRS-, and QT-intervals, that increase susceptibility to sudden cardiac death (SCD). However, the specific biophysical and molecular mechanisms that underlie the electrocardiograph (ECG) abnormalities and SCD in DM1 are unclear. Here, we addressed this issue using a novel transgenic mouse model that exhibits robust cardiac expression of expanded CUG-repeat RNA (LC15 mice). ECG measurements in conscious LC15 mice revealed significantly prolonged QRS- and corrected QT-intervals, but a normal PR-interval. Although spontaneous arrhythmias were not observed in conscious LC15 mice under nonchallenged conditions, acute administration of the sodium channel blocker flecainide prolonged the QRS-interval and unveiled an increased susceptibility to lethal ventricular arrhythmias. Current clamp measurements in ventricular myocytes from LC15 mice revealed significantly reduced action potential upstroke velocity at physiological pacing (9 Hz) and prolonged action potential duration at all stimulation rates (1-9 Hz). Voltage clamp experiments revealed significant rightward shifts in the voltage dependence of sodium channel activation and steady-state inactivation, as well as a marked reduction in outward potassium current density. Together, these findings indicate that expression of expanded CUG-repeat RNA in the murine heart results in reduced sodium and potassium channel activity that results in QRS- and QT-interval prolongation, respectively.
J Gen Physiol 2020 02 03
PMID:Biophysical mechanisms for QRS- and QTc-interval prolongation in mice with cardiac expression of expanded CUG-repeat RNA. 3196 60