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Neuromuscular Disorders 31 (2021) 1021–1027

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Review
Sarcoglycanopathies: an update
Mariz Vainzof a,∗, Lucas S. Souza a, Juliana Gurgel-Giannetti b, Mayana Zatz a
a Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São
Paulo, Brazil
b Department of Pediatrics, Service of Neuropediatrics from Federal, University of Minas Gerais, Belo Horizonte, Brazil

Received 23 June 2021; received in revised form 12 July 2021; accepted 16 July 2021

Abstract
Sarcoglycanopathies are the most severe forms of autosomal recessive limb-girdle muscular dystrophies (LGMDs), constituting about
10–25% of LGMDs. The clinical phenotype is variable, but onset is usually in the first decade of life. Patients present muscle hypertrophy,
elevated CK, variable muscle weaknesses, and progressive loss of ambulation. Four subtypes are known: LGMDR3, LGMDR4, LGMDR5
and LGMDR6, caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Their four coded proteins, α-SG, ß-SG,
λ-SG and δ-SG are part of the dystrophin-glycoprotein complex (DGC) present in muscle sarcolemma, which acts as a linker between the
cytoskeleton of the muscle fiber and the extracellular matrix, providing mechanical support to the sarcolemma during myofiber contraction.
Many different mutations have already been identified in all the sarcoglycan genes, with a predominance of some mutations in different
populations. The diagnosis is currently based on the molecular screening for these mutations. Therapeutic approaches include the strategy of
gene replacement mediated by a vector derived from adeno-associated virus (AAV). Pre-clinical studies have shown detectable levels of SG
proteins in the muscle, and some improvement in the phenotype, in animal models. Therapeutic trials in humans are ongoing.
© 2021 Published by Elsevier B.V.

Keywords: Limb girdle muscular dystrophies; SCARMD; Sarcoglycanopathies; DMD-like; Dystrophin-glycoprotein complex.

1. Introduction complex (DGC) [4,5], that acts as a linker between the

cytoskeleton of the muscle cell and the extracellular matrix,
The sarcoglycanopathies are usually the most severe providing mechanical support to the plasma membrane during
forms of limb-girdle muscular dystrophies (LGMD) [1,2], myofiber contraction. A role in cellular communication,
though with variable severity. The first name used for this as highlighted by its interaction with signaling molecules
clinical manifestation was SCARMD - severe childhood was also described [5,6]. The DGC is mainly composed
autosomal recessive muscular dystrophy, because of the by dystrophin, the dystroglycan and sarcoglycan complexes
phenotype similarity with Duchenne muscular dystrophy [7]. The sarcoglycan subcomplex is composed of at least
(DMD). Sarcoglycanopathies comprise four subtypes of four transmembrane glycoproteins: 50 kDa α-sarcoglycan,
autosomal recessive LGMD (LGMDR3, LGMDR4, LGMDR5 43 kDa ß-sarcoglycan, 35 kDa λ-sarcoglycan and 35 kDa δ-
and LGMDR6) that are caused, respectively, by mutations sarcoglycan. Two additional SG proteins, which are not
in the SGCA, SGCB, SGCG and SGCD genes. A new directly involved in the diagnosis of LGMD, are Epsilon-
nomenclature for the LGMD forms was proposed at the sarcoglycan (ε-SG) and Zeta-sarcoglycan (z-SG), present in
2nd ENMC workshop, 2017 [3], and the sarcoglycanopathies the smooth muscle SG complex. Mutations in the SGCE
subtypes are detailed in Table 1. gene have been identified in patients with myoclonus-dystonia
The sarcoglycan proteins are part of an important protein syndrome, an autosomal dominant non degenerative central
complex in muscle sarcolemma, the dystrophin-glycoprotein nervous system disorder [8–10].
It has been observed that the primary deficiency of
dystrophin in DMD leads to a secondary deficiency of
∗ Corresponding author. members of the DGC, implying that dystrophin is necessary
E-mail address: [email protected] (M. Vainzof).

https://doi.org/10.1016/j.nmd.2021.07.014
0960-8966/© 2021 Published by Elsevier B.V.
M. Vainzof, L.S. Souza, J. Gurgel-Giannetti et al. Neuromuscular Disorders 31 (2021) 1021–1027

Table 1 Online Archive of Brazilian Mutations (ABraOM – Arquivo

New and old nomenclature of the four sarcoglicanopathies. Brasileiro Online de Mutações [26]), including 1170 normal
New name Old name Locus Gene Protein elderly representing the Brazilian population. Using this
LGMDR3 LGMD2D 17q21 SGCA α-sarcoglycan bank, and considering only described pathogenic mutations
LGMDR4 LGMD2E 4q12 SGCB ß-sarcoglycan in the SG genes, we estimated the frequency of all the
LGMDR5 LGMD2C 13q12 SGCG λ-sarcoglycan sarcoglycanopathies as about 2.5/100,000 individuals in the
LGMDR6 LGMD2F 5q33 SGCD δ-sarcoglycan Brazilian population.
Regarding each subtype of the sarcoglycanopathies, we
estimated the following frequencies for the different SG
for the maintenance of the complex [11,12]. In most muscle genes: 0.9/100,000, 0.016/100,000 and 0.22/100,000 for
biopsies from patients with sarcoglycanopathy, the primary LGMDR3, LGMDR4 and LGMDR5 respectively. However,
loss or deficiency of any one of the four sarcoglycans, when we added the variants so far classified as VUS (Variant
ß- and δ-sarcoglycan in particular, leads to a secondary of Uncertain Significance) to the pathogenic/likely variants,
deficiency of the whole subcomplex [13–17]. However, the frequencies reach higher values: 4/100,000, 1.2/100,000,
exceptions may occur, such as the deficiency of γ -sarcoglycan 3/100,000 and 0.9/100,000 for LGMDR3, LGMDR4,
with a partial preservation of the other three sarcoglycans LGMDR5 and LGMDR6 respectively. Interestingly, most
in LGMDR5/LGMD2C [14] or the partial deficiency of of the variants found in the SGCD gene in our
only α-sarcoglycan with the retention of the other three in ABRaOM data bank were not found in gnomAD (https://
LGMDR3/LGMD2D [17,18]. The observation of a complete gnomad.broadinstitute.org) which might explain the rare
deficiency of one sarcoglycan with partial deficiency of the frequency of LRMD6 in non-Brazilians. In fact, whole
others has been used to suggest which gene should be first genome sequencing (WGS) analysis of our control population
screened for mutations before the advent of Next-generation identified about 2 million variants that were not present in
sequencing. other international data banks [27], illustrating the genetic
Patients with primary sarcoglycan mutations and deficiency variability of the different populations.
of the protein may have a secondary reduction in dystrophin Among patients with the severe phenotype, the frequency
as well, particularly patients with primary γ -sarcoglycan of sarcoglycanopathies ranges in various populations from
deficiency. This suggests that γ -sarcoglycan might interact between 22% and 69% of cases, whereas among adult-onset
more directly with dystrophin [14]. LGMD it is only 4–8% [2,20,28].
As to the relative proportion of each of the
2. Epidemiology sarcoglycanopathies, LGMDR3 is the most frequent form
in most countries, followed by LGMDR5 (which, however,
The sarcoglycanopathies represent the third most common is the most frequent form in Maghreb and India) and by
cause of AR-LGMD worldwide after the calpainopathies LGMDR4 and LGMDR6 [21]. In Europe and North America,
and dysferlinopathies [19], and constitute about 10–25% the LGMDR3 form is the most prevalent [21,29,30].
of cases in the majority of the countries, with higher The LGMDR5 form corresponds to almost 100% of the
frequency among inbred populations [20,21]. The frequency sarcoglycanopathies in Northern Africa [21] and is also the
of sarcoglycanopathies varies between different populations, most common form in the Aegean part of Turkey [31].
but it should be noted that LGMD patients with severe LGMDR4 is the most common form in patients from Iran
childhood-onset have a higher probability of ascertainment followed by LGMDR3 [32]. LGMDR6/2F seems to be
and obtaining a molecular diagnosis than those with adult- very rare all over the world. The four subtypes are well
onset [21]. It has been estimated in 15% in the American represented in Brazil, with the relative frequency of about
population, ∼25% in Italian patients [22], and accounts for 25% LGMDR5, 43% LGMDR3, 17% LGMDR4/2E and
about 32% of classified LGMD affected Brazilian patients 15% LGMDR6/2F [2,24].
[23,24]. However, it is a rare diagnosis among Indian patients, In 2016, the European Sarcoglycanopathy Consortium
with only five identified sarcoglycanopathy patients among was created with the aim to characterize the clinical
101 studied families [25]. Reported epidemiological studies and genetic spectrum of a large cohort of patients with
have estimated the prevalence of total sarcoglycanopathies sarcoglycanopathies in Europe. The study included a total
to be around 1/178,000 (0.56/100,000) and 1/370,000 of 33 neuromuscular centers from 13 different European
(0.27/100,000) inhabitants [19,21]. Also, the prevalence is countries and collected data from the genetically confirmed
variable in different countries, ranging from 3.4/100,000 patients with sarcoglycanopathies. In a recent study of this
(LGMDR3) to 0.07/ 100,000 (LGMDR6) [19]. group, important data on the genotype-phenotype correlation
In many countries, the frequency of the were presented, which are relevant for the design of natural
sarcoglycanopathies is difficult to be estimated due to history studies and upcoming interventional trials in the
the lack of a precise diagnosis in different centers. However, sarcoglycanopathies [30]. From a total of 439 patients,
NGS allows estimating the incidence of cases based on 159 patients had a confirmed diagnosis of LGMDR3, 73
the frequency of heterozygotes in genomic data banks of LGMDR4, 157 of LGMDR5 and seven of LGMDR6
from diverse populations. In Brazil, we generated the (Table 2).

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Table 2 hypertrophy including the tongue is frequent, creatine kinase

Frequency of sub-types of Sarcoglycanopathies in the different populations. levels are usually elevated to 10–100 times normal at least
LGMDR3 LGMDR4 LGMDR5 LGMDR6 N in active disease. A variable muscle weakness is observed
SGCA, SGCB SGCG SGCD (predominantly in the proximal muscles), difficulties in rising
European Cohort 159 73 157 7 396 from the floor (Gower’s sign), with progressive muscle
[30] 40% 18% 40% 2% weakness and loss of ambulation, frequently in the second
Brazil (actual 23 9 13 8 53 decade of life [33,34]. Cardiac and respiratory involvement
numbers) 43% 17% 25% 15%
Netherlands[53] 21 14 19 – 54
are not an early feature of the sarcoglycanopathies, but
39% 26% 35% both are present with the progression of the disease;
USA[54] 12 13 7 3 35 similarly to DMD. This cardiac involvement may be more
34% 37% 20% 8% prevalent with delta and beta sarcoglycanopathies but has
China[55] 27 7 1 – 35 been reported in association with mutations in alpha and
77% 20% 3%
gamma sarcoglycanopathy as well [13,21].
Clinical data of the 159 European patients [30] showed
3. Diagnosis that patients with LGMDR3 had a later onset and slower
progression of the disease. Cardiac involvement was most
In male patients, differential diagnosis with X- frequent in LGMDR4. Onset of symptoms before 10 years
linked Duchenne dystrophy, the most common form of of age and residual protein expression lower than 30% was
dystrophinopathy is achieved with the identification of associated to an independent risk factor for losing ambulation
a pathogenic mutation in the dystrophin gene (deletion/ before 18 years of age in LGMDR3/2D, LGMDR4/2E and
duplication by MLPA and point mutation detection by LGMDR5/2C patients.
NGS sequencing). Likewise, the distinction between
sarcoglycanopathy and milder cases of dystrophinopathy, 5. MRI in sarcoglycanopathies
such as Becker muscular dystrophy and manifesting
carriers of dystrophinopathy, also based on molecular The characterization of the pattern and spectrum of
analysis, is important as well. Before molecular diagnosis, involvement on muscle MRI was done in a large
particularly NGS, muscle biopsy analysis was very useful cohort of patients with sarcoglicanopathies, collected in 17
to suggest a diagnosis of sarcoglycanopathy through in neuromuscular referral centers in Europe and USA. Scans
situ muscle immunofluorescence or western blot analyses from 69 patients were examined (38 LGMDR3, 18 LGMDR5,
of the sarcoglycan proteins. However, muscle biopsy is an 12 LGMDR4 and 1 LGMDR6). A common pattern of
invasive procedure, and can be avoided when molecular involvement was found in all, irrespective of the mutated
diagnosis is informative. Moreover, given the multimeric gene. The most and earliest affected muscles were the
nature of the dystrophin-associated complex, the loss of one thigh adductors, glutei and posterior thigh groups and the
of the complex members usually causes a secondary loss or iliopsoas is typically early spared. Another important finding
at least reduction of the other complex members as well. was the sparing of the medial part of the adductor longus.
Currently, with the increased use of NGS molecular analysis. The lower leg muscles were relatively spared until loss of
all the involved genes can be studied simultaneously for a ambulation occurred. Also, even in advanced disease, the
differential diagnosis among all neuromuscular disorders. tibialis posterior and flexor digitorum longus are spared. A
However, protein investigation still can help to determine the proximodistal gradient of involvement of vasti muscles was a
pathogenicity of a VUS. consistent finding in these patients, including the most severe
ones. It was concluded that muscle involvement on MRI is
4. Clinical features consistent in patients with LGMDR3-6 and can be helpful
in distinguishing sarcoglycanopathies from other LGMDs or
Severe clinical DMD-like presentations tend to be more dystrophinopathies [35].
common among sarcoglycanopathies patients, with onset
occurring early in childhood and confinement to a wheelchair 6. Management
before the age of sixteen; nevertheless, milder courses have
also been described in LGMDR5, LGMDR3, and LGMDR4 The management principles for sarcoglycanopathies
patients as well as intrafamilial variability. It does not appear involve attention to strength and joint range of movement
that there are significant clinical distinguishing features in that require physiotherapy and, if necessary, orthopedic
the different sarcoglycanopathies. However, differently from intervention. Assessment of respiratory function will identify
dystrophinopathies they are not associated with intellectual the correct timing for nocturnal ventilatory support.
involvement or behavioral disturbances (such as Autism and Subclinical cardiac involvement is common and need to be
Attention deficit hyperactive disorder - ADHD). There is a monitored using echocardiography and eletrocardiography to
bias towards childhood rather than adult onset, though both the early identification of patients requiring treatment for
may be seen: for most patients with sarcoglycanopathy the cardiomyopathy [21]. Scoliosis may be a problem in the
onset occurs between 6 and 8 years. Calf and other muscle more severely affected patients, especially after the loss of

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Table 3 Similarly, the most common mutations in LMGDR5 patients

Gene characterization and variants in the SG genes–adapted from LOVD– were c.525delT or c.848G>A. In LGMDR4 patients the most
Leiden Open variation Database.
frequent mutation was c.341C>T [30].
Gene variants Unique variants update Associated disease Before the implementation of NGS methodologies, the
SGCA 953 224 2021-04-30 LGMDR3 characterization of each population was helpful, in order to
SGCB 520 144 2021-04-24 LGMDR4 select the gene, or mutations to be preferentially screened.
SGCG 710 175 2021-04-24 LGMDR5 In Brazil, the first report of the spectrum of mutations in 35
SGCD 221 103 2021-02-08 LGMDR6
SGCE 162 100 2021-02-08 DYT-11
Brazilian sarcoglycanopathy families showed the prevalence
SGCZ 16 14 2020-06-23 – of the following mutations: SGCA: exon 3, c.229C>T; SGCB:
mutations in exons 3/4; SGCG: exon 6, c.521delT; and
Table 4 SGCD: exon 7, c.656delC, corresponding to 78%, 75%, 100%
Type of mutations in the SG genes (According to the Human Gene Mutation and 80% of the disease alleles of the respective LGMD
Database – HGMD - http://www.hgmd.cf.ac.uk/ac/index.php). forms. Therefore, we implemented a multiplex methodology
Mutation type SCGA SCGB SCGG SCGD SGCE to screen these mutations in one unique test at the Human
Genome and Stem Cell Research Center, University of São
Missense/nonsense 69 28 14 16 30
Splicing 8 6 4 1 19 Paulo [40]. However, currently we apply Whole Exome
Regulatory 0 0 0 0 0 Sequencing, or specific panels for neuromuscular disorders
Small deletions 8 11 11 4 29 to screen simultaneously a huge number of genes for NMD.
Small insertions 7 6 5 0 6
Small indels 3 1 0 0 1
Gross deletions 3 4 20 2 29
Gross insertions/duplications 1 3 1 0 0 8. Genotype-Phenotype correlations
Complex rearrangements 0 0 1 0 1
Repeat variations 0 0 0 0 0 Severe Duchenne-like presentations tend to be relatively
Total 99 59 56 23 115 common among these patients, with onset occurring early in
childhood and confinement to a wheelchair before the age of
sixteen. Patients harboring null mutations in both alleles of
ambulation, requiring spinal surgery. The use of corticosteroid one of the SG genes, as well as a drastic decrease of the
medication is controversial, there are some anecdotal reports, entire SG complex, usually tend to show a severe phenotype,
but no controlled studies with large number of patients although there are exceptions. In the Brazilian population,
[29,36]. the majority of the severely affected LGMD patients have
sarcoglycanopathy [2]. Nevertheless, milder courses have
7. Genetics also been described in LGMDR5/2C, LGMDR3/2D, and
LGMDR4/2E patients.
Many different mutations have already been identified Most patients with missense changes in both alleles show
in all the sarcoglycan genes, including missense, splicing, a dramatic reduction of the primary protein levels together
nonsense, small and large gene deletions. A complete with variable deficiency of the secondary sarcoglycans. This
database can be consulted in LOVD–Leiden Open variation pattern has been associated usually with a severe clinical
Database (https:// www.lovd.nl/ http:// www.dmd.nl) (Table 3). course in LGMDR4 and LGMDR6 but with both mild and
Some mutations are prevalent in different populations, severe presentations in LGMDR3. Within this last subgroup,
such as the c.229C>T (p.Arg77Cys) in homozygosity or clinical variability among patients homozygous for the same
compound heterozygosity in SGCA. This mutation is the most mutation seems to correlate with the residual amount of γ -
frequent in the European and Brazilian populations. In fact, sarcoglycan in the muscle, despite the absence of the other
the frequency of this mutation in the ABraOM and gnomAD three sarcoglycans in all of them.
database is 0.000427 and 0.0004581, respectively. However, Most intriguing is the fact that a few frequent alterations,
the homozygous mutation c.525delT (p.Phe175Leufs∗ 20) in like c.229C>T (p.Arg77Cys) in the SGCA (LGMDR3) and
SGCG is prevalent in the African and in the Brazilian c.521delT in the SGCG genes have been associated with
population with African origin [14,37–39]. The frequency of both severe and mild forms. The study of the phenotype and
this mutation in the ABraOM database is of 0.000427, while sarcoglycan expression in 132 Tunisian LGMDR5 patients
it is lower in the gnomAD database (0.00003295). sharing the same c.del521T mutation showed heterogeneous
As to the type of mutations, the majority consists of phenotypes, even between siblings, which was encountered
missense mutations and small deletions. In SGCG and SGCE in 75% of the families. The phenotypic variability which was
gross deletions can also be found at a high frequency also observed in Brazilian families with the same mutation
(Table 4). [14] suggests the involvement of a modifying gene controlling
Frequency analysis of mutations in the European the course of the disease [41] or epigenetic mechanisms.
population showed that 60% of LGMDR3 patients carried Therefore, the establishment of precise genotype/phenotype
one of the following mutations, either in a homozygous correlations has proven to be a challenge for most researchers
or heterozygous state: c.229C>T, c.739G>A or c.850C>T. working on sarcoglycanopathies [24].

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9. Therapeutic perspectives and several muscle-specific promoters were tested [49,50].

Currently, trials using gene therapy are ongoing for different
Over the last 3 decades, the possibility of gene editing neuromuscular disorders (NMD) such as DMD and X-linked
aiming to provide an effective treatment for many inherited myotubular myopathy. SMA (Spinal Muscle Atrophy) is a
human diseases with a durable and possibly curative successful example of NMD treated with gene therapy that
clinical benefit with a single treatment, has been pursued is already approved for commercial use in different countries
by different investigators. As autosomal recessive diseases, and illustrates the potential for the broader application of AAV
sarcoglycan mutations normally result from a loss of delivery vectors.
function of the protein, making gene replacement a suitable As for the sarcoglycanopathies, some studies were done
therapeutic approach. Local injections in sarcoglycanopathy in small group of patients, using local injections, with the
patientsḿuscles have been among the first gene therapy trials main objective of testing doses, adverse effects, and the
to be performed in neuromuscular diseases. For preclinical expression of the missing proteins in LGMDR3/2D [49] and
studies, sarcoglycanopathy mice models, both knockout or LGMDR5/2C [51].
carrying different mutations is the SG genes were created [42– More recently, the group of Dr. J. Mendell transferred
44], with some of them expressing clinical aspects observed the α-sarcoglycan (αSG) gene into six LGMDR3/2D
in human patients. Canine models have also been identified, subjects using scAAVrh74.tMCK.hSGCA vector in different
including the finding of two independent mutations in SGCD doses, using unilateral or bilateral vascular limb infusion
in Boston terrier dogs. [45,46]. . In four biopsied patients, SGCA gene delivery was
Gene therapy using adeno-associated virus (AAV) is one confirmed by immunofluorescence, Western blot analysis (14–
of the preferred methods because the gene delivered by this 25% of normal), and vector genome copies (5.4 × 103–
vector does not integrate into the patient genome and has low 7.7 × 104 vg/μg). Muscle strength in the knee extensors
immunogenicity. The proof of principle of the effectiveness (assessed by force generation in kilograms) showed
of such a strategy aiming at restoring the phenotype of mice improvement in two subjects that correlated with an increase
deficient in sarcoglycans have been reported in a large number in fiber diameter post gene delivery. Six-minute walk times
of experiments, and is revised in [19]. These preclinical decreased or remained the same. Limb infusion delivery of
studies have been the basis of several clinical trials with AAVrh74.tMCK.hSGCA was effective at producing SGCA
different modes of administration (intramuscular injection, protein at low doses that correlated with vector copies
limb infusion or systemic injection). In many of them it and local functional improvement restricted to targeted
was possible to detect levels of sarcoglycan expression in muscles. Future trials of the group will focus on systemic
the muscle, and some improvement in the phenotype. Such administration to enable targeting of proximal muscles to
preclinical tests can provide relevant information particularly maximize clinical benefit [49]. Additional protocols of gene
taking into account the constant improvement of the involved delivery clinical trial also for LGMDR4 are currently ongoing
vectors. Indeed, a recent publication on the systemic Delivery (NIH ClinicalTrials.gov).
of Adeno-Associated α-Sarcoglycan Gene Transfer in the In conclusion, the results obtained in clinical trials using
sgca-null (sgca-/-) mouse showed a robust expression of α- gene therapy along the last 20 years are encouraging is
sarcoglycan protein at the muscle sarcolemma, improvement spite of their use in small groups of patients mainly
of the histopathology of limb and diaphragm muscles, and because of phenotypic heterogeneity of the patients. Several
resulted in a significant increase in specific force generation studies are ongoing and pharmaceutical companies, such as
and locomotor activity. These data provide support for a Sarepta Therapeutics has a program that includes therapy
systemic delivery of scAAVrh74.tMCK.hSGCA in a clinical protocols for LGMDR3, LGMDR4 and LGMDR5/2C. The
setting for the treatment of LGMD2D [47] .Experiments French Genethon, is also preparing a protocol using systemic
with autologous muscle stem cells injections, after ex- administration for α and λ sarcoglycan in the near future [19].
vivo correction of the mutation, are also ongoing [48]. On the other hand, some limitations, and adverse effects, such
The researchers isolated human muscle stem cells from as severe complications in the XLMTM trial require further
two patients with the common SGCA c.157G>A mutation. studies. The efficacy and safety in each disease certainly will
Through Adenine base editing (ABE), they corrected the require further analysis and long-term follow-up [52].
mutation with > 90% efficiency, rescuing the defect and α-
sarcoglycan expression. These cells were then intramuscular Declaration of Competing Interest
transplanted in a xenograft model mouse, and were able to
regenerate the muscle and contributed to the Pax7+ satellite All the authors declare no conflict of interest.
cell compartment in vivo. This represents a good example of
the possibility of an autologous gene–repaired human muscle Acknowledgments
stem cells for muscular dystrophy cell replacement therapies.
In humans, gene delivery clinical trials using viral vector We would like to thank the support from the NGS
injected in muscles from affected patients have been done Diagnostic Laboratory and the help from the professionals
since 2000. The studies have shown a long-term and sustained of the Human Genome and Stem Cells Research Center.
gene expression of the injected gene mediated by AAV, Thisworkwassupportedby Fundação de Amparo à Pesquisa do

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Estado de São Paulo - Centro de Pesquisa, Inovação e Difusão https://doi.org/10.1002/(SICI)1097-0029(20000201/15)48:3/4<167::

(FAPESP-CEPID, Grant 2013/8028-1), Conselho Nacional AID−JEMT5>3.0.CO;2-T.
de Desenvolvimento Cientıfico e Tecnológico (CNPq-INCT, [17] Bönnemann CG, Finkel RS. Sarcolemmal proteins and the spectrum of
limb-girdle muscular dystrophies. Semin Pediatr Neurol 2002;9:81–99.
Grant 465355/2014-5), Financiadora de Estudos e Projetos doi:10.1053/spen.2002.33795.
(FINEP). CAPES – Coordenação de aperfeiçoamento de [18] Vainzof M, Moreira ES, Canovas M, Anderson LVB,
Pessoal de Nivel Superior. Pavanello RCM, Passos-Bueno MR, et al. Partial α-sarcoglycan
deficiency with retention of the dystrophin- glycoprotein
complex in a LGMD2D family. Muscle Nerve 2000;23:984–8
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