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Developmental Dynamics : An Official... Mar 2016The muscles of the shoulder region are important for movements of the upper limbs and for stabilizing the girdle elements by connecting them to the trunk. They have a... (Review)
Review
The muscles of the shoulder region are important for movements of the upper limbs and for stabilizing the girdle elements by connecting them to the trunk. They have a triple embryonic origin. First, the branchiomeric shoulder girdle muscles (sternocleidomastoideus and trapezius muscles) develop from the occipital lateral plate mesoderm using Tbx1 over the course of this development. The second population of cells constitutes the superficial shoulder girdle muscles (pectoral and latissimus dorsi muscles), which are derived from the wing premuscle mass. This muscle group undergoes a two-step development, referred to as the "in-out" mechanism. Myogenic precursor cells first migrate anterogradely into the wing bud. Subsequently, they migrate in a retrograde manner from the wing premuscle mass to the trunk. SDF-1/CXCR4 signaling is involved in this outward migration. A third group of shoulder muscles are the rhomboidei and serratus anterior muscles, which are referred to as deep shoulder girdle muscles; they are thought to be derived from the myotomes. It is, however, not clear how myotome cells make contact to the scapula to form these two muscles. In this review, we discuss the development of the shoulder girdle muscle in relation to the different muscle groups.
Topics: Animals; Avian Proteins; Chick Embryo; Humans; Limb Buds; Mesoderm; Muscle, Skeletal; Myoblasts, Skeletal; Shoulder; Signal Transduction; Wings, Animal
PubMed: 26676088
DOI: 10.1002/dvdy.24378 -
Indian Pediatrics Nov 2003The best known muscular dystrophies are X-linked dystrophinopathies. A clinically and genetically heterogeneous group presenting with weakness of the pelvic and shoulder...
The best known muscular dystrophies are X-linked dystrophinopathies. A clinically and genetically heterogeneous group presenting with weakness of the pelvic and shoulder girdles is that of the limb-girdle muscular dystrophies (LGMDs). Sarcoglycanopathies (SGPs) are autosomal recessive LGMDs. We report a rare case of primary gamma-sarcoglycanopathy (SGP) which emphasizes the evolving concept of dystrophinopathy to sarco-glycanopathy.
Topics: Biopsy, Needle; Child; Cytoskeletal Proteins; Genes, Recessive; Humans; Immunohistochemistry; India; Male; Muscle, Skeletal; Muscular Dystrophies; Prognosis; Sarcolemma
PubMed: 14660840
DOI: No ID Found -
Arquivos de Neuro-psiquiatria Sep 2014Limb girdle muscular dystrophies are heterogeneous autosomal hereditary neuromuscular disorders. They produce dystrophic changes on muscle biopsy and they are associated... (Review)
Review
Limb girdle muscular dystrophies are heterogeneous autosomal hereditary neuromuscular disorders. They produce dystrophic changes on muscle biopsy and they are associated with mutations in several genes involved in muscular structure and function. Detailed clinical, laboratorial, imaging, diagnostic flowchart, photographs, tables, and illustrated diagrams are presented for the differential diagnosis of common autosomal recessive limb girdle muscular dystrophy subtypes diagnosed nowadays at one reference center in Brazil. Preoperative image studies guide muscle biopsy site selection. Muscle involvement image pattern differs depending on the limb girdle muscular dystrophy subtype. Muscle involvement is conspicuous at the posterior thigh in calpainopathy and fukutin-related proteinopathy; anterior thigh in sarcoglycanopathy; whole thigh in dysferlinopathy, and telethoninopathy. The precise differential diagnosis of limb girdle muscular dystrophies is important for genetic counseling, prognostic orientation, cardiac and respiratory management. Besides that, it may probably, in the future, provide specific genetic therapies for each subtype.
Topics: Biopsy; Diagnosis, Differential; Female; Humans; Male; Medical Illustration; Muscles; Muscular Dystrophies, Limb-Girdle; Tomography, X-Ray Computed; Ultrasonography
PubMed: 25252238
DOI: 10.1590/0004-282x20140110 -
Acta Myologica : Myopathies and... May 2015Different genetic mutations underlying distinct pathogenic mechanisms have been identified as cause of muscle fibers degeneration and strength loss in limb girdle... (Review)
Review
Different genetic mutations underlying distinct pathogenic mechanisms have been identified as cause of muscle fibers degeneration and strength loss in limb girdle muscular dystrophies (LGMD). As a consequence, exercise tolerance is affected in patients with LGMD, either as a direct consequence of the loss of muscle fibers or secondary to the sedentary lifestyle due to the motor impairment. It has been debated for many years whether or not muscle exercise is beneficial or harmful for patients with myopathic disorders. In fact, muscular exercise would be considered in helping to hinder the loss of muscle tissue and strength. On the other hand, muscle structural defects in LGMD can result in instability of the sarcolemma, making it more likely to induce muscle damage as a consequence of intense muscle contraction, such as that performed during eccentric training. Several reports have suggested that supervised aerobic exercise training is safe and may be considered effective in improving oxidative capacity and muscle function in patients with LGMD, such as LGMD2I, LGMD2L, LGMD2A. More or less comfortable investigation methods applied to assess muscle function and structure can be useful to detect the beneficial effects of supervised training in LGMD. However, it is important to note that the available trials assessing muscle exercise in patients with LGMD have often involved a small number of patients, with a wide clinical heterogeneity and a different experimental design. Based on these considerations, resistance training can be considered part of the rehabilitation program for patients with a limb-girdle type of muscular dystrophy, but it should be strictly supervised to assess its effects and prevent possible development of muscle damage.
Topics: Exercise; Exercise Tolerance; Female; Humans; Male; Muscle Fatigue; Muscle, Skeletal; Muscular Dystrophies, Limb-Girdle; Mutation; Sarcolemma
PubMed: 26155063
DOI: No ID Found -
Acta Myologica : Myopathies and... 2022Limb-girdle muscular dystrophy (LGMD) is a genetic muscle disorder causing weakness and wasting of the proximal limb musculature. When ambulation is lost, the attention...
Limb-girdle muscular dystrophy (LGMD) is a genetic muscle disorder causing weakness and wasting of the proximal limb musculature. When ambulation is lost, the attention must be shifted to the upper limb muscles' function. We studied the upper limb muscle strength and the corresponding function in 15 LGMDR1/LGMD2A and 13 LGMDR2/LGMD2B, through the Performance of Upper Limb scale and the MRC score of upper limbs. The proximal item K and the distal items N and R were lower in LGMD2B/R2. The mean MRC score of all the muscles involved linearly correlated (r2 = 0.922) for item K in LGMD2B/R2. The functional worsening paralleled the muscles weakness in LGMD2B/R2. By contrast, at proximal level the function of LGMD2A/R1 was preserved despite muscle weakness was present, presumably due to compensatory strategies. Sometimes the combination of parameters might be more informative than considering them separately. PUL scale and MRC might be interesting outcome measures in non-ambulant patients.
Topics: Humans; Muscular Dystrophies, Limb-Girdle; Muscle, Skeletal; Muscle Weakness; Upper Extremity
PubMed: 36793650
DOI: 10.36185/2532-1900-084 -
The Protein Journal Aug 2021The limb-girdle muscular dystrophies (LGMD) are a collection of genetic diseases united in their phenotypical expression of pelvic and shoulder area weakness and... (Review)
Review
The limb-girdle muscular dystrophies (LGMD) are a collection of genetic diseases united in their phenotypical expression of pelvic and shoulder area weakness and wasting. More than 30 subtypes have been identified, five dominant and 26 recessive. The increase in the characterization of new genotypes in the family of LGMDs further adds to the heterogeneity of the disease. Meanwhile, better understanding of the phenotype led to the reconsideration of the disease definition, which resulted in eight old subtypes to be no longer recognized officially as LGMD and five new diseases to be added to the LGMD family. The unique variabilities of LGMD stem from genetic mutations, which then lead to protein and ultimately muscle dysfunction. Herein, we review the LGMD pathway, starting with the genetic mutations that encode proteins involved in muscle maintenance and repair, and including the genotype-phenotype relationship of the disease, the epidemiology, disease progression, burden of illness, and emerging treatments.
Topics: Genotype; Humans; Muscular Dystrophies, Limb-Girdle; Mutation
PubMed: 34110586
DOI: 10.1007/s10930-021-10006-9 -
Neurotherapeutics : the Journal of the... Oct 2018There has been an ever-expanding list of the Limb-Girdle Muscular Dystrophies (LGMD). There are currently 8 subtypes of autosomal dominant (AD) and 26 subtypes of... (Review)
Review
There has been an ever-expanding list of the Limb-Girdle Muscular Dystrophies (LGMD). There are currently 8 subtypes of autosomal dominant (AD) and 26 subtypes of autosomal recessive (AR) LGMD. Despite continued research efforts to conquer this group of genetic neuromuscular disease, patients continue to be treated symptomatically with the aim of prevention or addressing complications. Mouse models have been helpful in clarifying disease pathogenesis as well as strategizing pathways for treatment. Discoveries in translational research as well as molecular therapeutic approaches have kept clinicians optimistic that more promising clinical trials will lead the way to finding the cure for these devastating disorders. It is well known that the challenge for these rare diseases is the ability to assemble adequate numbers of patients for a clinically meaningful trial, but current efforts in developing patient registries have been encouraging. Natural history studies will be essential in establishing and interpreting the appropriate outcome measures for clinical trials. Nevertheless, animal studies continue to be key in providing proof of concept that will be necessary in moving research along. This review will briefly discuss each type of LGMD, highlighting their distinguishing features, then focus on research efforts that have been published in the literature for the past few years, many of which are still in the preclinical trial stage.
Topics: Animals; Humans; Muscular Dystrophies, Limb-Girdle
PubMed: 30019308
DOI: 10.1007/s13311-018-0648-x -
PloS One 2020Positional information on the shoulder girdle (the clavicle and scapula) is important for a better understanding of the function of the upper limb in the locomotive...
Positional information on the shoulder girdle (the clavicle and scapula) is important for a better understanding of the function of the upper limb in the locomotive system as well as its associated disease pathogenesis. However, such data are limited except for information on the axial position of the scapula. Here, we describe a three-dimensional reconstruction of the shoulder girdle including the clavicle and scapula, and its relationship to different landmarks in the body. Thirty-six human fetal specimens (crown-rump length range: 7.6-225 mm) from the Kyoto Collection were used for this study. The morphogenesis and three-dimensional position of the shoulder girdle were analyzed with phase-contrast X-ray computed tomography and magnetic resonance imaging. We first detected the scapula body along with the coracoid and humeral head at Carnegie stage 18; however, the connection between the body and coracoid was not confirmed at this stage. During development, all landmarks on the shoulder girdle remained at the same axial position except for the inferior angle, which implies that the scapula enlarged in the caudal direction and reached the adult axial position in the fetal period. The scapula body was rotated internally and in the upward direction at the initiation of morphogenesis, but in the fetal period the scapula body was different than that in the adult position. The shoulder girdle was located at the ventral side of the vertebrae at the time of initial morphogenesis, but changed its position to the lateral side of the vertebrae in the late embryonic and fetal periods. Such a unique position of the shoulder girdle may contribute to the stage-specific posture of the upper limb. Adequate internal and upward rotation of the scapula could help in reducing the shoulder width, thereby facilitating childbirth. The data presented in this study can be used as normal morphometric references for shoulder girdle evaluations in the embryonic and fetal periods.
Topics: Fetal Development; Growth and Development; Humans; Range of Motion, Articular; Shoulder; Shoulder Joint; Upper Extremity
PubMed: 32915841
DOI: 10.1371/journal.pone.0238225 -
Skeletal Muscle May 2023Limb-girdle muscular dystrophy R8 (LGMD R8) is a rare autosomal recessive muscle disease caused by TRIM32 gene biallelic defects. The genotype-phenotype correlation of...
BACKGROUND
Limb-girdle muscular dystrophy R8 (LGMD R8) is a rare autosomal recessive muscle disease caused by TRIM32 gene biallelic defects. The genotype-phenotype correlation of this disease has been reported poorly. Here, we report a Chinese family with two female LGMD R8 patients.
METHODS
We performed whole-genome sequencing (WGS) and Sanger sequencing on the proband. Meanwhile, the function of mutant TRIM32 protein was analyzed by bioinformatics and experimental analysis. In addition, a summary of the reported TRIM32 deletions and point mutations and an investigation of genotype-phenotype correlation were performed through a combined analysis of the two patients and other cases reported in previous literature.
RESULTS
The two patients displayed typical symptoms of LGMD R8, which worsened during pregnancy. Genetic analysis by whole-genome sequencing (WGS) and Sanger sequencing showed that the patients were compound heterozygotes of a novel deletion (chr9.hg19:g.119431290_119474250del) and a novel missense mutation (TRIM32:c.1700A > G, p.H567R). The deletion encompassed 43 kb and resulted in the removal of the entire TRIM32 gene. The missense mutation altered the structure and further affected function by interfering with the self-association of the TRIM32 protein. Females with LGMD R8 showed less severe symptoms than males, and patients carrying two mutations in NHL repeats of the TRIM32 protein had earlier disease onset and more severe symptoms than other patients.
CONCLUSIONS
This research extended the spectrum of TRIM32 mutations and firstly provided useful data on the genotype-phenotype correlation, which is valuable for the accurate diagnosis and genetic counseling of LGMD R8.
Topics: Male; Female; Humans; Muscular Dystrophies, Limb-Girdle; Mutation; Genetic Association Studies; Muscular Diseases; Mutation, Missense; Tripartite Motif Proteins; Transcription Factors; Ubiquitin-Protein Ligases
PubMed: 37217920
DOI: 10.1186/s13395-023-00319-x -
Genes Sep 2022Anoctaminopathy-5 refers to a group of hereditary skeletal muscle or bone disorders due to mutations in the anoctamin 5 (ANO5)-encoding gene, . ANO5 is a 913-amino acid... (Review)
Review
Anoctaminopathy-5 refers to a group of hereditary skeletal muscle or bone disorders due to mutations in the anoctamin 5 (ANO5)-encoding gene, . ANO5 is a 913-amino acid protein of the anoctamin family that functions predominantly in phospholipid scrambling and plays a key role in the sarcolemmal repairing process. Monoallelic mutations in give rise to an autosomal dominant skeletal dysplastic syndrome (gnathodiaphyseal dysplasia or GDD), while its biallelic mutations underlie a continuum of four autosomal recessive muscle phenotypes: (1). limb-girdle muscular dystrophy type R12 (LGMDR12); (2). Miyoshi distal myopathy type 3 (MMD3); (3). metabolic myopathy-like (pseudometabolic) phenotype; (4). asymptomatic hyperCKemia. ANO5 muscle disorders are rare, but their prevalence is relatively high in northern European populations because of the founder mutation c.191dupA. Weakness is generally asymmetric and begins in proximal muscles in LGMDR12 and in distal muscles in MMD3. Patients with the pseudometabolic or asymptomatic hyperCKemia phenotype have no weakness, but conversion to the LGMDR12 or MMD3 phenotype may occur as the disease progresses. There is no clear genotype-phenotype correlation. Muscle biopsy displays a broad spectrum of pathology, ranging from normal to severe dystrophic changes. Intramuscular interstitial amyloid deposits are observed in approximately half of the patients. Symptomatic and supportive strategies remain the mainstay of treatment. The recent development of animal models of ANO5 muscle diseases could help achieve a better understanding of their underlying pathomechanisms and provide an invaluable resource for therapeutic discovery.
Topics: Animals; Muscular Dystrophies, Limb-Girdle; Anoctamins; Muscular Diseases; Muscle, Skeletal; Phospholipids; Amino Acids
PubMed: 36292621
DOI: 10.3390/genes13101736