Generally, presentation varies with the type of LGMD involved, however, typical features include proximal muscle weakness (distal involvement in some cases), leading to difficulty ambulating, waddling gait, and hypotonia. Some patients, however present with mild facial paresis [12] [13] [14] [15]. Lower limb muscles commonly affected the adductors, psoas, and quadriceps while the deltoid, triceps, and biceps are most commonly affected in the upper limbs.

The first symptom to be noticed in LGMD is muscle weakness noticed as difficulty walking, carrying objects, lifting the arms, and an unstable gait. The onset of presentation varies with the individual and the type of genetic mutation involved. In most autosomal recessive cases, however, presentation begins at a young age and occur with a slow progression and significant complications. Distal muscle strength is almost always preserved.

Most cases of LGMD present with mainly proximal weakness affecting the biceps, neck muscles, and facial muscles. Extraocular muscles are not affected in LGMD. However, LGMD may present with low back pain [16] [17]. Some cases present with dysmotility of the esophagus and delayed motor development in children.

Although, intellectual impairment is generally absent in LGMD, a few cases present with mental retardation.

• Difficulty Climbing Stairs

  Generally, the first symptom that people with limb-girdle muscular dystrophy will notice is muscle weakness that causes trouble walking, resulting in a "waddling" gait and difficulty climbing stairs or getting up from chairs. [sharecare.com]

  Examples of this include trouble standing from a sitting position without using the arms, or difficulty climbing stairs. The weakness starts in childhood to young adulthood. [nlm.nih.gov]

  Loss of ability to perform transfers Decreased endurance and tolerance to activity Difficulty climbing stairs and lifting objects Unable to do overhead activities with progressive difficulty for self-care and movements Scoliosis / Lordosis Dysphagia may [physio-pedia.com]

• Unable to Stand

  They are usually unable to stand without using their own body to steady themselves and, as such, present with Gower’s sign (where patients use their own hands to push off the thighs when rising from the floor). They may also waddle. [lecturio.com]

• Respiratory Insufficiency

  Six patients had restrictive respiratory insufficiency requiring assisted ventilation (19%). Seventeen different mutations were identified, and 3 were recurrent. [ncbi.nlm.nih.gov]

  Pulmonary: Some subtypes are at increased risk for restrictive lung disease leading to respiratory insufficiency due to respiratory muscle weakness; these patients plus those with scoliosis should have routine pulmonary function tests. [now.aapmr.org]

  Respiratory Symptoms - Early intervention to treat respiratory insufficiency with non-invasive ventilation can help improve function and prolong the patient's life expectancy. [physio-pedia.com]

  May have cardiac and respiratory complications - in some cases, the cardiac muscle is more affected than the skeletal muscle; [ 26 ] diaphragmatic involvement may cause respiratory insufficiency while still ambulant. [patient.info]

  Sometimes, respiratory insufficiency may manifest exclusively as increased susceptibility to respiratory infections, matinal headache, and daily somnolence, due to nocturnal hypoxia 19. [doi.org]

• Muscle Weakness

  Progressive proximal muscle weakness began again at age 8 years. Serum CK was 14,910 IU/L. She was wheelchair-bound by age 12. [ncbi.nlm.nih.gov]

  In addition to proximal muscle weakness, there may or may not be: Distal muscle weakness. Muscle hypertrophy. Contractures. Involvement of the heart, respiratory muscles or tongue. (Facial weakness is not usual.) [patient.info]

  […] treatments that reverse the muscle weakness. [nlm.nih.gov]

• Myopathy

  For this reason our finding extends the histological spectrum of myopathies due to ANO5 mutations as well as the possible differential diagnoses for necrotizing myopathy. [ncbi.nlm.nih.gov]

  Some mutations can cause both a myofibrillar myopathy and a muscular dystrophy phenotype. [emedicine.com]

• Proximal Muscle Weakness

  Progressive proximal muscle weakness began again at age 8 years. Serum CK was 14,910 IU/L. She was wheelchair-bound by age 12. [ncbi.nlm.nih.gov]

  In addition to proximal muscle weakness, there may or may not be: Distal muscle weakness. Muscle hypertrophy. Contractures. Involvement of the heart, respiratory muscles or tongue. (Facial weakness is not usual.) [patient.info]

• Muscular Atrophy

  Our results indicate that alterations in the protein turnover and myostatin levels could progressively impair the muscle mass maintenance and/or regeneration resulting in gradual muscular atrophy. [ncbi.nlm.nih.gov]

  […] of voluntary muscles, ultimately termed pseudohypertrophic muscular paralysis of children by Duchenne.1,2 Other descriptions followed: familial atrophy of the pelvic girdle muscles (Leyden in 1876), scapulohumeral muscular atrophy (Erb in 1884), and [dash.harvard.edu]

  Atrophy (SMA) Center Stiff Person Syndrome Center Transverse Myelitis Center Trigeminal Neuralgia Center Vestibular Disorders In This Section The Limb Girdle muscular dystrophies (LGMD) comprise at least a dozen different specific entities. [hopkinsmedicine.org]

  A heterogeneous group of genetic disorders characterized by progressive muscular atrophy and muscle weakness beginning in the hands, the legs, or the feet. Most are adult-onset autosomal dominant forms. Others are autosomal recessive. [icd10data.com]

  A novel autosomal recessive limb-girdle muscular dystrophy with quadriceps atrophy maps to 11p13–p12. Brain 130, 368–380 (2007). 36. Bolduc, V. et al. [nature.com]

• Lordosis

  Skeletal abnormalities - Abnormal posture due to weakness of muscles can lead to scoliosis/lordosis/kyphosis in later stages can be corrected via orthopedic procedures like spinal decompression, spinal fusion, spinal correction. [physio-pedia.com]

  Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. [lgmd-info.org]

  Affected individuals may also have an abnormally curved lower back ( lordosis ) or a spine that curves to the side ( scoliosis ). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. [ghr.nlm.nih.gov]

• Waddling Gait

  We report a Saudi Arabian family with weakness in limb-girdle distribution: waddling gait, positive Gowers' sign, and marked muscle atrophy in the shoulder and pelvic girdle muscles. [ncbi.nlm.nih.gov]

  Generally, the first symptom that people with limb-girdle muscular dystrophy will notice is muscle weakness that causes trouble walking, resulting in a "waddling" gait and difficulty climbing stairs or getting up from chairs. [sharecare.com]

  Inability to rise to an upright position without turning to the side, waddling gait, and progressive weakness are the characteristic features. Pseudohypertrophy of the calf muscles is due to fibrous tissue and fat infiltration. [icd9data.com]

  Generally, presentation varies with the type of LGMD involved, however, typical features include proximal muscle weakness (distal involvement in some cases), leading to difficulty ambulating, waddling gait, and hypotonia. [symptoma.com]

  Muscle wasting Slow progression Intelligence and cognition is usually normal Waddling gait - weakness of hip musculature, gait dysfunction, foot drop Scapular Winging Joint stiffness Contractures Frequent falls Difficulty walking for longer distances [physio-pedia.com]

• Limb Weakness

  PATIENT CONCERNS: A 25-year-old woman was admitted to our department as the limb weakness progressively worsened. [ncbi.nlm.nih.gov]

  Usually, there is lower limb weakness that, after a period of about 6 years, is followed by upper limb weakness, but this interval may vary from 1 to 16 years 35. [doi.org]

• Foot Drop

  One case is reported as presenting with foot drop - aged 41. [ 24 ] LGMD 2B (dysferlin) also known as Miyoshi myopathy Late teens, early 20s May have distal myopathy (Miyoshi myopathy). Markedly elevated CKs. [patient.info]

  Muscle wasting Slow progression Intelligence and cognition is usually normal Waddling gait - weakness of hip musculature, gait dysfunction, foot drop Scapular Winging Joint stiffness Contractures Frequent falls Difficulty walking for longer distances [physio-pedia.com]

  Occasionally, leg weakness may involve the anterior compartment and cause foot drop [ Illa et al 2001 ]. Elevated serum CK concentration only. Some individuals have only a marked elevation of serum CK concentration. [ncbi.nlm.nih.gov]

  Observation of the gait can reveal signs of distal weakness such as foot drop or an inability to walk on toes. Examination of facial extraocular muscules also should be conducted. [healio.com]

• Gowers Sign

  We report a Saudi Arabian family with weakness in limb-girdle distribution: waddling gait, positive Gowers' sign, and marked muscle atrophy in the shoulder and pelvic girdle muscles. [ncbi.nlm.nih.gov]

  Image : “Gower’s sign.” by William Richard Gowers (1845–1915) – Gowers WR. Clinical lecture on pseudohypertrophic muscular paralysis. Lancet 1879;ii,73-5. [lecturio.com]

  Is there a finding (or history) of Gower's sign? This is seen in patients with proximal muscle weakness of the lower limb: when rising to stand, they use the hands as support, such that the hands 'climb up the legs'. [patient.info]

  […] ability to perform transfers Decreased endurance and tolerance to activity Difficulty climbing stairs and lifting objects Unable to do overhead activities with progressive difficulty for self-care and movements Scoliosis / Lordosis Dysphagia may occur Gower's [physio-pedia.com]

• Dysarthria

  Fasciculation and atrophy of the tongue with dysphagia, dysarthria, and thickened nasal speech are usually associated. [icd9data.com]

  The muscles of the respiratory system may also become involved in some cases resulting in difficulty swallowing (dysphagia), slurred speech (dysarthria), and breathing difficulties. [rarediseases.org]

  Onset CK Level Progression Muscular Findings Extramuscular Findings LGMD1A MYOT/Myotilin Adulthood Normal to High Slow Scapular-humeral-pelvic Distal Weakness; Rimmed vacuole; Ankle contractures Peripheral Neuropathy; Cardiomyopathy; Nasal speech / dysarthria [now.aapmr.org]

  Myotilin): Distal weakness 1B (LMNA): Cardiac arrhythmias 1C (CAV3): Mainly rippling muscles & Myalgias 1E & 2R (Desmin): Distal weakness; Cardiomyopathy 2V : Glycogen storage disease LGMD: Previous classification LGMD1: Dominant 1A : Myotilin; 5q31; Dysarthria [neuromuscular.wustl.edu]

Genetic testing is the first investigation of choice in the diagnosis of LGMD. Individual or single gene testing is indicated if there are typical phenotypic features of suspected muscular dystrophies. For example, genetic testing for LGMD1 is indicated in all patients with duchene or becker muscular dystrophic phenotypes and LMNA gene testing should be done in patients with Emery-Dreifuss type muscular dystrophies.

Muscle biopsy is indictated if gene testing is unavailable or inconclusive. Immunohistochemical techniques testing antibodies directed against certain genes are employed to identify the specific genetic mutation from the biopsy sample [18]. Serum CK is neither sensitive nor specific for LGMD as it shows varying results, however, it may be particularly elevated in some forms of LGMD.

DNA analysis is the investigation of choice in the diagnosis of LGMD, although, its use varies with the forms of LGMD. Other useful tests in the diagnosis of LGMD include MRI, which helps differentiate the various forms of LGMD based on signal changes on T1 weighted scans, Electromyography (EMG) and routine ECG. The EMG should be done in all patients with suspected LGMD and it serves to reveal the typical findings of the myopathy. Moreover, the ECG identifies, excludes, and follows up cases with cardiac involvement.

• Muscle Biopsy Abnormal

  Muscle biopsy abnormalities in two individuals very early in the course of their disease suggest that biopsy would probably be useful in detection of preclinical disease in this type of muscular dystrophy. [pediatrics.aappublications.org]

Treatment of LGMD is mainly supportive as no treatment can correct the underlying genetic abberation. Supportive treatment involves preserving muscle function, preventing complications, and reducing morbidity. Complications of LGMD include contractures, scoliosis, and cardiac arrhythmias. Cardiac arrhythmias are mostly seen in LGMD 1B and 1E types of muscle dystrophy.

Cardiopulmonary compromise may be corrected early with intermittent positive pressure ventilation bilevel positive airway pressure ( BiPAP) or continuous positive airway pressure (CPAP). A pacemaker may be necessary in patients who develop arrhythmias. In those who develop heart failure, cardiac transplant has resulted in significant reduction in mortality rates [19] [20].

Preliminary studies have shown responsiveness of the disease to low impact aerobic exercises such as cycling and swimming, and glucocorticoid therapy [21] [22]. 

Studies are underway to analyse the benefits of gene transfer and exon skipping as treatment modalities for LGMD [23] [24] [25]. Home remedies which show significant benefit in alleviating symptoms in LGMD include massage and warm baths to maintain muscle strength, balanced diet with a lot of proteins, and reducing stress on the muscle by shedding excess fats in overweight patients.

Support groups, occupational therapy, and physical therapy play very vital roles in the management of these disorders. Stretch exercises to strengthen the affected muscles are instituted by physiotherapists. Surgical correction may be needed for the skeletal complications.

By and large, the management of LGMD is a multidisciplinary task involving a cardiologist, pulmunologist, orthopedic surgeon, neurologist, and a physiotherapist.

Prognosis of LGMD depends on the type of muscular dystrophy and involvement of the cardiac and respiratory muscles. The disease progresses at varying rates, even between individuals with the same type of dystrophy [2]. Therefore, the lifespan of the patient is largely dependent on the disease progression and, in turn, on the type of LGMD involved.

Mortality in LGMD is caused by respiratory failure, cardiomyopathy, and arrhythmias. Cardiac complications are most commonly seen in the LGMD 1B and 1E types.

All types of LGMD are genetic disorders with varying defects but mainly affecting the proteins of the muscle cell membranes. The genetic defects make the muscles dysfunctional, eventially causing weakness and atrophy of the muscles.

Most LGMDs are autosomal recessive disorders [4]. Whereas some are inherited in an autosomal dominant pattern, the pattern of inheritance of the rest are unknown [5] [6]. Genetic mutations involved in LGMD include mutations in POMT1 and 2, caveolin 3 gene, dysferlin gene, LARGE, FKRP, POMT1titin, fukutin, and POMGnT1 genes.

Mutations in the caveolin 3 gene mostly cause distal myopathy, rather than the typical proximal myopathy. Mutations in the dysferlin gene cause many types of muscular dystrophies including LGMD and Miyoshi distal myopathy [7]. Generally, the myopathies caused by this mutation are collectively termed dysferlinopathies. Mutations in the FKRP, LARGE, POMT1 and 2, and POMGnT1 genes cause a spectrum of autosomal recessive dystrophies called dystroglycanopathies [8] [9]. The dystroglycanopathies have a lot of similarities and are caused by genetic defects in the glycosylation of the extracellular alpha-dystroglycan receptor.

Mutations in sarcoglycan genes cause sarcoglycanopathies, which are autosomal recessive muscular dystrophies [10]. There are alpha, beta, gamma, and delta sarcoglycan genes which are affected in this group of muscular dystrophies. The sarcoglycanopathies include LGMD2C, LGMD2D, LGMD2F, and LGMD2E. Generally, the sacroglycanopathies typically present very early.

LGMDs are very rare disorders, with the autosomal recessive forms more common than the dominant types which make up about 10% of the LGMDs. LGMDs show no racial nor gender disparities and present at different ages depending on the mutation involved. Onset of presentation usually occurs before the age of 50 years, although some disorders present as late as the sixth decade of life. Generally, the earlier the onset of presentation, the more rapid the course of the disease.

In 2009, a study conducted in Northern England revealed an incidence rate of 2 in 100,000 individuals in that year with 68 out of 2.99 million persons reported to be diagnosed with LGMD [11].

Limb-girdle muscular dystrophy (LGMD) results from genetic mutations affecting the proteins required for muscle function including the proteins associated with sarcolemma and contractility. While the genetic mutations are identified, the pathophysiology behind the signs and symptoms of the muscle dystrophy is not well understood.

LGMD being genetic disorders cannot be prevented, however genetic testing may lead to early diagnosis and treatment in individuals with a family history of LGMD.

LGMD is a group of muscle disorders which are all due to genetic mutations affecting muscle function. These disorders present with different features and at different ages, however, typical symptoms include proximal muscle weakness affecting the muscles of the arms, shoulders, hips, and thighs [1].

These disorders are caused by different genetic mutations, which determine the severity of the disease, rate of progression and prognosis of the disease. There are individual variations in the presentation and severity of symptoms in patients with similar types of muscular dystrophy [2]. Complications of LGMD include contractures, scoliosis, lordosis, respiratory failure, and cardiomyopathy. Scapular winging may also occur because of the weakness of the pectoral girdle muscles.

Most LGMDs are autosomal recessive disorders and have several subtypes with similar groups of genes affected [3]. Genetic testing, DNA studies, and muscle biopsy are modalities of choice in the diagnosis of these diseases.

Treatment of LGMD is largely supportive with the aim of management being to reduce morbidity, prevent or correct complications, and improve quality of life for affected individuals.

Overview.

Limb-girdle muscular dystrophy are a group of genetic disorders of the muscles causing weakness and reduction in muscle size, particularly affecting the muscles of the shoulder and hips.

Etiology.

LGMD are caused by mutations in the genes. The genes are units in human chromosomes which encode every structure in the body and every information about the body. Any abberation occuring to any of the genes would affect the structures and information encoded. In the case of LGMD, the genes involved in proper muscle function are mutated and abnormal. There are a lot of disorders which make up the LGMD and each is caused by a different genetic mutation. However, the processes through which these genetic mutation cause abnormal functioning of the muscles are unknown.

Prognosis.

The severity and outcome of these group of disorders depends on the genetic mutation and the particular type of disorder involved. However, death occurs in these disorders if the disease progresses to affect the muscles of the heart and those which help us breathe. This, in turn, may lead to breathing problems and abnormalities in the heart beat. 

The prognosis varies in that some types of LGMD present with early onset of symptoms and death at a tender age, while some may make the patient disabled for a very long time before leading to death.

Presentation.

Although the symptoms and signs of these disorders depend on the type of LGMD in question, they mostly cause weakness and loss of function of the muscles of the arms and shoulders causing difficulty carrying objects and lifting the arms. The muscles of the hips and thighs are also affected causing unstable gait, and difficulty in walking, eventually necessitating a wheelchair. 

LGMDs may present with difficulty swallowing and abnormal facial appearance such as drooping of one side of the mouth.

Some complications of these disorders include sticking out of the shoulder blade (called winging of the shoulder blade due to the weak shoulder muscles), abnormal curvature of the spine of the lower back, and joint stiffness. More serious complications that could arise are the weakening of the heart muscles and muscles required for breathing, as mentioned above, these could cause breathing problems and difficulties with the heart pump.

Although this group of disorders doesn't affect the patient's intellect, a few cases have been noted to be associated with mental retardation.

Epidemiology.

Most of these disorders are inherited in autosomal recessive way, that is, the two copies of the gene in both chromosomes (the chromosomes are arranged in pairs, hence the genes are paired) involved must be affected for the disease to manifest. However, some of them are inherited with just one copy of the gene affected, these are called autosomal dominant diseases.

This group of diseases doesn't have gender preferences as it affects both males and females equally. In addition, LGMD affects persons of all races.

Workup.

To diagnose these disorders, testing the genetic makeup of the muscle cells is important. Since it would be difficult testing all the genes involved in all these diseases, it is better to test for particular genes based on the suspected disorder as can be determined by the prevailing signs and symptoms. Muscle biopsy involving using a big needle to take small pieces from the muscles is also essential in the diagnosis of these disorders.

It is also essential to conduct an investigation called electrocardiogram (ECG) which detects the abnormalities in the heart caused by these disorders. 

Treatment.

There is no treatment for the genetic disorders. Treatment is therefore largely supportive, which means, the symptoms are just managed and complications are prevented. Physiotherapy and occupational therapy would be instituted to strengthen the affected muscles and enable the patient handle daily activities.

Treatment would involve a lot of medical specialists working in concert. Physicians who specialize in managing conditions of the the heart, lungs, brain, orthopedic surgeons, and physiotherapists would be involved in the management. Early medical care such as inserting a device that stimulates the heart to pump, known as a pacemker, and providing assisted respiration would be necessary if the heart and the lungs, respectively, are compromised. Surgery may be recommended to correct skeletal deformities which result from LGMD.

1. Guglieri M, Bushby K. How to go about diagnosing and managing the limb-girdle muscular dystrophies. Neurol India. 2008 Jul-Sep;56(3):271-80.
2. EFNS guideline on diagnosis and management of limb girdle muscular dystrophies, European Federation of Neurological Societies (2007).
3. Rosales XQ, Tsao CY. Childhood onset of limb-girdle muscular dystrophy. Pediatr Neurol. 2012 Jan;46(1):13-23. doi: 10.1016/j.pediatrneurol.2011.08.014.
4. Zatz M, de Paula F, Starling A, Vainzof M. The 10 autosomal recessive limb-girdle muscular dystrophies. Neuromuscul Disord 2003; 13:532.
5. Kirschner J, Bönnemann CG. The congenital and limb-girdle muscular dystrophies: sharpening the focus, blurring the boundaries. Arch Neurol 2004; 61:189.
6. Gordon, E, Pegoraro, E, Hoffman, EP. Limb-girdle muscular dystrophy overview. www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=lgmd-overview (Accessed on September 17, 2010).
7. Nguyen K, Bassez G, Krahn M, et al. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Arch Neurol 2007; 64:1176.
8. Godfrey C, Clement E, Mein R, et al. Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. Brain 2007; 130:2725.
9. Muntoni F, Torelli S, Brockington M. Muscular dystrophies due to glycosylation defects. Neurotherapeutics 2008; 5:627.
10. Bonnemann CG. The limb girdle muscular dystrophies. In: Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician's Approach, Jones HR, De Vivo DC, Darras BT (Eds), Butterworth-Heinemann, Philadelphia 2003. p.717.
11. Norwood FL, Harling C, Chinnery PF, Eagle M, Bushby K, Straub V. Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population. Brain. Nov 2009;132(Pt 11):3175-3186.
12. Emery AE: The muscular dystrophies. BMJ 317(7164):991-5. 1998 Oct 10.
13. Norwood F, de VM, Eymard B, Lochmuller H, Bushby K: EFNS guideline on diagnosis and management of limb girdle muscular dystrophies. Eur J Neurol 2007, 14(12):1305-12.
14. Brockington M, Blake DJ, Prandini P, Brown SC, Torelli S, Benson MA, et al.: Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha2 deficiency and abnormal glycosylation of alpha-dystroglycan. Am J Hum Genet 2001, 69(6):1198-209.
15. Kirschner J, Bonnemann CG. The congenital and limb-girdle muscular dystrophies: sharpening the focus, blurring the boundaries. Arch Neurol 2004, 61(2):189-99.
16. Dubowitz V. Muscle Biopsy: A Practical Approach. Bailliere Tindall, London 1985. p.289.
17. Brooke MH. Limb-girdle dystrophy. In: A Clinician's View of Neuromuscular Diseases, Brooke MH (Ed), Williams and Wilkins, Baltimore 1986. p.178.
18. Charlton R, Henderson M, Richards J, et al. Immunohistochemical analysis of calpain 3: advantages and limitations in diagnosing LGMD2A. Neuromuscul Disord 2009; 19:449.
19. Ambrosi P, Mouly-Bandini A, Attarian S, Habib G. Heart transplantation in 7 patients from a single family with limb-girdle muscular dystrophy caused by lamin A/C mutation. Int J Cardiol 2009; 137:e75.
20. Margeta M, Connolly AM, Winder TL, et al. Cardiac pathology exceeds skeletal muscle pathology in two cases of limb-girdle muscular dystrophy type 2I. Muscle Nerve 2009; 40:883.
21. Sveen ML, Jeppesen TD, Hauerslev S, et al. Endurance training: an effective and safe treatment for patients with LGMD2I. Neurology 2007; 68:59.
22. Godfrey C, Escolar D, Brockington M, et al. Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy. Ann Neurol 2006; 60:603.
23. Rodino-Klapac LR, Lee JS, Mulligan RC, et al. Lack of toxicity of alpha-sarcoglycan overexpression supports clinical gene transfer trial in LGMD2D. Neurology 2008; 71:240.
24. Mendell JR, Rodino-Klapac LR, Rosales XQ, et al. Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. Ann Neurol 2010; 68:629.
25. Wein N, Avril A, Bartoli M, et al. Efficient bypass of mutations in dysferlin deficient patient cells by antisense-induced exon skipping. Hum Mutat 2010; 31:136.