Limb‐girdle muscular dystrophy: A perspective from adult patients on what matters most

Hunter, Michael; Heatwole, Chad; Wicklund, Matthew; Weihl, Conrad C.; Mozaffar, Tahseen; Statland, Jeffrey; Johnson, Nicholas E.

doi:10.1002/mus.26636

Cited by 17 publications

(15 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…They can develop conditions in early childhood, adolescence or adulthood, and the probability of onset is equal between men and women. Patients suffering LGMDs have diverse disease progression, with contractures, scoliosis, cardiopulmonary involvement and distal limb weakness commonly being observed 5 …”

Section: Discussionmentioning

confidence: 99%

“…Patients suffering LGMDs have diverse disease progression, with contractures, scoliosis, cardiopulmonary involvement and distal limb weakness commonly being observed. 5 LGMDs encompass autosomal dominant (LGMD1) and recessive forms (LGMD2) based on genetic patterns and disease-causing genes. LGMDs are the inherited diseases with highly clinical heterogeneity, the ise of serum CK level, EMG, muscle biopsy, MRI and molecular genetic testing may contribute to a timely diagnosis for patients.…”

Section: Bioinformatic Analysis Of Dysf Variantsmentioning

confidence: 99%

“…The limb‐girdle muscular dystrophies (LGMDs), comprsing the fourth most common muscular dystrophies only after myotonic dystrophy type I, Duchenne muscular dystrophy and facioscapulohumeral dystrophy, can affect people of any age and often worsen over time, mostly characterized by progressive wasting and weakness of the proximal limb muscles, predominantly involving pelvic and shoulder girdle muscles, with an estimated prevalence of 0.8–5.7 per 100,000 individuals 2,4–7 . The phenotypic spectrum of LGMDs varies significantly as a result of genetic heterogeneity, ranging from a very mild form in adults without serious impact on life expectancy and activity levels to a severe form in infants with rapid onset and progression 8–10 .…”

Section: Introductionmentioning

confidence: 99%

“…individuals. 2,[4][5][6][7] The phenotypic spectrum of LGMDs varies significantly as a result of genetic heterogeneity, ranging from a very mild form in adults without serious impact on life expectancy and activity levels to a severe form in infants with rapid onset and progression. [8][9][10] Additionally, patients with LGMDs may present respiratory and cardiac muscles degeneration, distal limb weakness, uncommon mental deficiency, microcephaly, contractures, scoliosis and motor impairment that involves abnormal gait, frequent falling, running disability and difficulty in climbing stairs.…”

mentioning

confidence: 99%

“…[8][9][10] Additionally, patients with LGMDs may present respiratory and cardiac muscles degeneration, distal limb weakness, uncommon mental deficiency, microcephaly, contractures, scoliosis and motor impairment that involves abnormal gait, frequent falling, running disability and difficulty in climbing stairs. 4,5,7,11,12 To date, LGMDs can be further divided into eight autosomal dominant (LGMD1;…”

mentioning

confidence: 99%

See 4 more Smart Citations

Compound heterozygous DYSF variants causing limb‐girdle muscular dystrophy type 2B in a Chinese family

Jing

Cheng

et al. 2020

The Journal of Gene Medicine

View full text Add to dashboard Cite

Background: The dysferlin gene or the DYSF gene encodes the Ca 2+-dependent phospholipid-binding protein dysferlin, which belongs to the ferlin family and is associated with muscle membrane regeneration and repair. Variants in the DYSF gene are responsible for limb-girdle muscular dystrophy type 2B (LGMD2B), also called limb-girdle muscular dystrophy recessive 2 (LGMDR2), a rare subtype of muscular dystrophy involving progressive muscle weakness and atrophy. The present study aimed to identify the variants responsible for the clinical symptoms of a Chinese patient with limb girdle muscular dystrophies (LGMDs) and to explore the genotypephenotype associations of LGMD2B. Methods: A series of clinical examinations, including blood tests, magnetic resonance imaging scans for the lower legs, electromyography and muscle biopsy, was performed on the proband diagnosed with muscular dystrophies. Whole exome sequencing was conducted to detect the causative variants, followed by Sanger sequencing to validate these variants. Results: We identified two compound heterozygous variants in the DYSF gene, c.1058 T>C, p.(Leu353Pro) in exon 12 and c.1461C>A/p.Cys487* in exon 16 in this proband, which were inherited from the father and mother, respectively. In silico analysis for these variants revealed deleterious results by PolyPhen-2 (Polymorphism Phenotyping v2; http://genetics.bwh.harvard.edu/pph2), SIFT (Sorting Intolerant From Tolerant; https://sift.bii.a-star.edu.sg), PROVEAN (Protein Variation Effect Analyzer; http://provean.jcvi.org/seq_submit.php) and MutationTaster (http://www. mutationtaster.org). In addition, the two compound heterozygous variants in the proband were absent in 100 control individuals who had an identical ethnic origin and were from the same region, suggesting that these variants may be the pathogenic variants responsible for the LGMD2B phenotypes for this proband. Conclusions: The present study broadens our understanding of the mutational spectrum of the DYSF gene, which provides a deep insight into the pathogenesis of LGMDs and accelerates the development of a prenatal diagnosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Bioinformatic Analysis Of Dysf Variantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Compound heterozygous DYSF variants causing limb‐girdle muscular dystrophy type 2B in a Chinese family

Jing

Cheng

et al. 2020

The Journal of Gene Medicine

View full text Add to dashboard Cite

show abstract

A Journey with LGMD: From Protein Abnormalities to Patient Impact

Georganopoulou¹,

Moisiadis²,

Malik³

et al. 2021

Protein J

View full text Add to dashboard Cite

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.

show abstract

Concept Elicitation Interviews and Conceptual Model to Understand the Patient Experience of Limb Girdle Muscular Dystrophy

et al. 2023

View full text Add to dashboard Cite

Introduction Limb girdle muscular dystrophies (LGMDs) are a group of rare and heterogeneous disorders involving progressive wasting of shoulder and pelvic girdle musculature. This study aimed to generate qualitative evidence on patient and caregiver experiences with symptoms and impacts of LGMD on overall function and daily life for sarcoglycanopathy subtypes 2C/R5, 2D/R3, and 2E/R4. Methods Twenty-three individuals with LGMD with ( n = 5) or without ( n = 18) a caregiver participated in 60-minute semi-structured video interviews. Interview transcripts were analyzed using thematic analysis. Differences in patient experience by ambulation status and LGMD subtype were examined. Results Participants were ambulatory ( n = 14) and non-ambulatory ( n = 9), representing three subtypes: 2C/R5 ( n = 4), 2D/R3 ( n = 12), and 2E/R4 ( n = 7), with mean age of 34.8 years (SD = 16.08). 56.5% identified as female. Conceptual saturation was achieved within 18/23 interviews. Ambulatory participants identified difficulty with complex physical activities, e.g., running ( n = 11, 78.6%), physical strength ( n = 14, 100%), and difficulty with transfers, e.g., difficulty getting off the floor ( n = 10, 71.4%). All non-ambulatory participants discussed problems with activities of daily living (ADLs) and transfers, e.g., getting in/out of bed and upper extremity function, particularly reaching ( n = 8, 88.9%) and fine motor skills ( n = 6, 66.7%). Fatigue and pain were reported by the majority of participants ( n = 16, 69.6% and n = 19, 82.6%, respectively). A conceptual disease model was developed illustrating symptoms and impacts and their relationships to disease stage, capturing the patient experience across LGMD disease trajectory. Conclusions This study contributes to the limited evidence describing the patient experience of living with LGMD. The conceptual model can inform patient-centered assessment in future LGMD clinical trials.

show abstract

Limb‐girdle muscular dystrophy: A perspective from adult patients on what matters most

Cited by 17 publications

References 34 publications

Compound heterozygous DYSF variants causing limb‐girdle muscular dystrophy type 2B in a Chinese family

Compound heterozygous DYSF variants causing limb‐girdle muscular dystrophy type 2B in a Chinese family

A Journey with LGMD: From Protein Abnormalities to Patient Impact

Concept Elicitation Interviews and Conceptual Model to Understand the Patient Experience of Limb Girdle Muscular Dystrophy

Contact Info

Product

Resources

About