Prevalence, pathological mechanisms, and genetic basis of limb‐girdle muscular dystrophies: A review

Taghizadeh, Eskandar; Rezaee, Mehdi; Barreto, George E.; Sahebkar, Amirhossein

doi:10.1002/jcp.27907

Cited by 57 publications

(81 citation statements)

References 97 publications

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“…The minimum prevalence of AR‐LGMD and MMD cases in the Netherlands amounted to 14.4 × 10 −6 individuals which is similar to the prevalence in the United Kingdom and less than in Italy . In our study, we found similar frequencies of AR‐LGMD and MMD subtypes to what is reported in Eastern, Central and Southern Europe but differs from the United Kingdom and Denmark.…”

Section: Discussionsupporting

confidence: 83%

Autosomal recessive limb‐girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients

Dam

Frankhuizen

Linssen³

et al. 2019

Clinical Genetics

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In this retrospective study, we conducted a clinico‐genetic analysis of patients with autosomal recessive limb‐girdle muscular dystrophy (LGMD) and Miyoshi muscular dystrophy (MMD). Patients were identified at the tertiary referral centre for DNA diagnosis in the Netherlands and included if they carried two mutations in CAPN3, DYSF, SGCG, SGCA, SGCB, SGCD, TRIM32, FKRP or ANO5 gene. DNA was screened by direct sequencing and multiplex ligand‐dependent probe amplification (MLPA) analysis. A total of 244 patients was identified; 68 LGMDR1/LGMD2A patients with CAPN3 mutations (28%), 67 sarcoglycanopathy patients (LGMDR3‐5/LGMD2C‐E) (27%), 64 LGMDR12/LGMD2L and MMD3 patients with ANO5 mutations (26%), 25 LGMDR2/LGMD2B and MMD1 with DYSF mutations (10%), 21 LGMDR9/LGMD2I with FKRP mutations (9%) and one LGMDR8/LGMD2H patient with TRIM32 mutations (<1%). The estimated minimum prevalence of AR‐LGMD and MMD in the Netherlands amounted to 14.4 × 10−6. Thirty‐three novel mutations were identified. A wide range in age of onset (0‐72 years) and loss of ambulation (5‐74 years) was found. Fifteen patients (6%) initially presented with asymptomatic hyperCKemia. Cardiac abnormalities were found in 35 patients (17%). Non‐invasive ventilation was started in 34 patients (14%). Both cardiac and respiratory involvement occurs across all subtypes, stressing the need for screening in all included subtypes.

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Section: Discussionsupporting

confidence: 83%

Autosomal recessive limb‐girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients

Dam

Frankhuizen

Linssen³

et al. 2019

Clinical Genetics

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“…Dystrophin, alpha-dystroglycan and sarcoglycan play important roles in maintaining sarcolemma stability and muscle integrity as the dystrophinglycoprotein complex 2 . Pathogenic variants in causative genes of sarcoglycanopathy lead to loss-of-function effects in different members of the skeletal muscle sarcoglycan complex and cause LGMD 2C, 2D, 2E and 2F 10 . However, pathogenic variants in FKRP lead to glycosylation defects in alpha-dystroglycan 10 .…”

Section: Introductionmentioning

confidence: 99%

“…Pathogenic variants in causative genes of sarcoglycanopathy lead to loss-of-function effects in different members of the skeletal muscle sarcoglycan complex and cause LGMD 2C, 2D, 2E and 2F 10 . However, pathogenic variants in FKRP lead to glycosylation defects in alpha-dystroglycan 10 . Mechanisms in each disorder are different.…”

Section: Introductionmentioning

confidence: 99%

Duchenne muscular dystrophy–like phenotype in an LGMD2I patient with novel FKRP gene variants

et al. 2020

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A 32-year-old man initially received a diagnosis of Duchenne muscular dystrophy (DMD). Genetic analysis revealed two novel heterozygous FKRP variants: c.169G>A (p.Glu57Lys) and c.692G>A (p.Trp231*). These results indicated that the patient had limb-girdle muscular dystrophy type 2I (LGMD2I) caused by recessive FKRP variants. Patients with LGMD2I and DMD have many overlapping phenotypes. LGMD2I should be considered in patients who have a DMD phenotype but not a DMD pathogenic variant.

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“…Mutations in collagen 6α led to severe Ulrich CMD or milder Bethlem myopathy [ 24 ]. MDs showed genetic heterogeneity by sharing different clinical manifestations with the mutations in different genes, such as nine known genes associated with Emery–Dreifuss muscular dystrophy [ 30 ] and twenty-six known genes associated with limb-girdle muscular dystrophy [ 31 ]. Due to overlapping clinical symptoms and the multiple possible genetic causes for MDs and CMDs, it is difficult to obtain an accurate diagnosis for patients [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family

Nguyen

Ngọc

et al. 2020

Diagnostics

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Muscular dystrophies are a group of heterogeneous clinical and genetic disorders. Two siblings presented with characteristics like muscular dystrophy, abnormal white matter, and elevated serum creatine kinase level. The high throughput of whole exome sequencing (WES) makes it an efficient tool for obtaining a precise diagnosis without the need for immunohistochemistry. WES was performed in the two siblings and their parents, followed by prioritization of variants and validation by Sanger sequencing. Very rare variants with moderate to high predicted impact in genes associated with neuromuscular disorders were selected. We identified two pathogenic missense variants, c.778C>T (p.H260Y) and c.2987G>A (p.C996Y), in the LAMA2 gene (NM_000426.3), in the homozygous state in two siblings, and in the heterozygous state in their unaffected parents, which were confirmed by Sanger sequencing. Variant c.2987G>A has not been reported previously. These variants may lead to a change in the structure and function of laminin-α2, a member of the family of laminin-211, which is an extracellular matrix protein that functions to stabilize the basement membrane of muscle fibers during contractions. Overall, WES enabled an accurate diagnosis of both patients with LAMA2-related muscular dystrophy and expanded the spectrum of missense variants in LAMA2.

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Prevalence, pathological mechanisms, and genetic basis of limb‐girdle muscular dystrophies: A review

Cited by 57 publications

References 97 publications

Autosomal recessive limb‐girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients

Autosomal recessive limb‐girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients

Duchenne muscular dystrophy–like phenotype in an LGMD2I patient with novel FKRP gene variants

Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family

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