Clinical Determinants of Disease Progression in Patients With Beta-Sarcoglycan Gene Mutations

Marchetti, Giulia; Valenti, Luca; Torrente, Yvan

doi:10.3389/fneur.2021.657949

Cited by 6 publications

(7 citation statements)

References 26 publications

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“…Despite small sample sizes, this systematic literature review demonstrated findings aligned with a recent Italian retrospective study of 26 patients with LGMDR4, published after the period of the current review. 147 As observed in the systematic review, the age at which respiratory support was required for patients with LGMDR4 also preceded the age at which cardiac support was required in this study (mean age: 20 and 22 years, respectively). In addition, LOA occurred before respiratory and cardiac support in the retrospective study (mean age: 15 years).…”

Section: Clinical Neuromuscular Diseasesupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

“…Several factors could underlie this difference, for example, the higher number of cardiological compared with pneumological visits in the retrospective study (1.5 and 1.3, respectively). 147 Among LGMDR patients with LOA, the occurrence of respiratory and cardiac involvement was observed among those of all subtypes except for LGMDR12. Regardless of subtype, patients with LOA often had respiratory and/or cardiac involvement, although the frequency of involvement varied widely.…”

Section: Clinical Progression In Autosomal Recessivementioning

confidence: 91%

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Patterns of Clinical Progression Among Patients With Autosomal Recessive Limb-Girdle Muscular Dystrophy: A Systematic Review

Cheung,

Audhya,

Szabo

et al. 2023

Journal of Clinical Neuromuscular Disease

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Objectives: As the clinical course of autosomal recessive limb–girdle muscular dystrophy (LGMDR) is highly variable, this study characterized the frequency of loss of ambulation (LOA) among patients by subtype (LGMDR1, LGMDR2, LGMDR3–6, LGMDR9, LGMDR12) and progression to cardiac and respiratory involvement among those with and without LOA. Methods: Systematic literature review. Results: From 2929 abstracts screened, 418 patients were identified with ambulatory status data (LOA: 265 [63.4%]). Cardiac and/or respiratory function was reported for 142 patients (34.0%; all with LOA). Among these, respiratory involvement was most frequent in LGMDR3–6 (74.1%; mean [SD] age 23.9 [11.0] years) and cardiac in LGMDR9 (73.3%; mean [SD] age 23.7 [17.7] years). Involvement was less common in patients without LOA except in LGMDR9 (71.4% respiratory and 52.4% cardiac). Conclusions: This study described the co-occurrence of LOA, cardiac, and respiratory involvement in LGMDR and provides greater understanding of the clinical progression of LGMDR.

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Section: Clinical Neuromuscular Diseasesupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Clinical Progression In Autosomal Recessivementioning

confidence: 91%

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Patterns of Clinical Progression Among Patients With Autosomal Recessive Limb-Girdle Muscular Dystrophy: A Systematic Review

Cheung,

Audhya,

Szabo

et al. 2023

Journal of Clinical Neuromuscular Disease

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“…Cardiac involvement is frequent in LGMDR4; more than 60% of LGMDR4 patients suffer from dilated cardiomyopathy [ 16 ], with onset of cardiac involvement at around 25 years of age [ 6 , 7 ]. A recent study confirmed the higher prevalence of dilated cardiomyopathy in LGMDR4 presenting mono- or biallelic SGCB c.377_384dup [ 17 ], strengthening the existence of a phenotype–genotype correlation. In our patient, initial cardiac involvement was observed at the age of 16 years.…”

Section: Discussionmentioning

confidence: 75%

Antisense Morpholino-Based In Vitro Correction of a Pseudoexon-Generating Variant in the SGCB Gene

Magri

Zanotti

Salani

et al. 2022

IJMS

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Limb-girdle muscular dystrophies (LGMD) are clinically and genetically heterogenous presentations displaying predominantly proximal muscle weakness due to the loss of skeletal muscle fibers. Beta-sarcoglycanopathy (LGMDR4) results from biallelic molecular defects in SGCB and features pediatric onset with limb-girdle involvement, often complicated by respiratory and heart dysfunction. Here we describe a patient who presented at the age of 12 years reporting high creatine kinase levels and onset of cramps after strenuous exercise. Instrumental investigations, including a muscle biopsy, pointed towards a diagnosis of beta-sarcoglycanopathy. NGS panel sequencing identified two variants in the SGCB gene, one of which (c.243+1548T>C) was found to promote the inclusion of a pseudoexon between exons 2 and 3 in the SGCB transcript. Interestingly, we detected the same genotype in a previously reported LGMDR4 patient, deceased more than twenty years ago, who had escaped molecular diagnosis so far. After the delivery of morpholino oligomers targeting the pseudoexon in patient-specific induced pluripotent stem cells, we observed the correction of the physiological splicing and partial restoration of protein levels. Our findings prompt the analysis of the c.243+1548T>C variant in suspected LGMDR4 patients, especially those harbouring monoallelic SGCB variants, and provide a further example of the efficacy of antisense technology for the correction of molecular defects resulting in splicing abnormalities.

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“…With the emerging possibilities of genetic therapies, interest in the detailed natural history of the disease is obvious [10][11][12][13][14][15][16]. Of the >500 genetically confirmed TMD patients in Finland, we were able to obtain follow-up data over 15 years of disease evolution in 137 patients.…”

Section: Introductionmentioning

confidence: 99%

Long‐term favorable prognosis in late onset dominant distal titinopathy: Tibial muscular dystrophy

Lillback

Savarese

Sandholm

et al. 2023

Euro J of Neurology

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Background and purpose Tibial muscular dystrophy (TMD) is a dominant late onset distal titinopathy. It was first described in Finnish patients 3 decades ago. TMD patients with several other TTN mutations occur in many European populations. In this retrospective study, we were able to obtain longitudinal follow‐up data of the disease progression over 15 years in 137 TMD patients. Methods We retrieved clinical data retrospectively from three examinations spanning a period of 15 years. The data were analyzed in R. Frequencies, percentages, and median values were used to describe data. Probability values were determined with the chi‐squared test. Results In the cohort, the first symptoms were walking difficulties (97.8%) and weakness in distal lower limbs (98.5%). The progression of the weakness in distal lower limbs was moderate, and in the proximal lower limbs and proximal upper limbs it was mild. The distal upper limbs were not affected. Magnetic resonance imaging results indicated fatty degeneration preferentially in lower leg anterior muscles, gluteus minimus, and hamstring muscles. Serum creatine kinase values in the cohort were mostly normal (40.7%) or mildly elevated (53.7%). The data suggest that 50% of patients need walking aids by the age of 88 years. Conclusions Despite individual variability of severity, the overall disability due to walking difficulties and upper limb weakness remained moderate even at very advanced ages, and cardiomyopathy did not develop due to the titin defect alone. The acquired results promote the correct identification of TMD, and the obtained trajectories of disease evolution can be used as natural history data for any therapeutic intervention.

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Clinical Determinants of Disease Progression in Patients With Beta-Sarcoglycan Gene Mutations

Cited by 6 publications

References 26 publications

Patterns of Clinical Progression Among Patients With Autosomal Recessive Limb-Girdle Muscular Dystrophy: A Systematic Review

Patterns of Clinical Progression Among Patients With Autosomal Recessive Limb-Girdle Muscular Dystrophy: A Systematic Review

Antisense Morpholino-Based In Vitro Correction of a Pseudoexon-Generating Variant in the SGCB Gene

Long‐term favorable prognosis in late onset dominant distal titinopathy: Tibial muscular dystrophy

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