Skeletal Muscle Laminopathies: A Review of Clinical and Molecular Features

Maggi, Lorenzo; Carboni, Nicola; Bernasconi, Pia

doi:10.3390/cells5030033

Cited by 73 publications

(63 citation statements)

References 83 publications

(127 reference statements)

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“…CK levels greater than 10 times the upper limit are associated with DMD, and BMD [19]. EMG is not required for diagnosis [20, 21]. Histological findings are nonspecific, displaying variability in muscle fibre diameters [20] as in our case.…”

Section: Discussionmentioning

confidence: 91%

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Occurrence of Emery-Dreifuss muscular dystrophy in a rural setting of Cameroon: a case report and review of the literature

et al. 2017

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BackgroundEmery-Dreifuss muscular dystrophy is a rare genetic muscular disease, presenting mainly with contractures, weakness and cardiac conduction abnormalities. Its clinical and laboratory similarities to other muscular dystrophies, and rarity poses diagnostic challenges, requiring a high index of suspicion in resource limited settings.Case presentationAn 8 year old sub-Saharan male presented with rigidity and deformity of both elbows and ankles, and weakness of the upper limbs and lower limbs for duration of 4 months. This progressed to inability to stand and walk. There was no mental impairment. Physical examination was remarkable for contractures of the elbows and ankles, and wasting of muscles of the limbs and trunk, with a scapulohumeroperoneal pattern, and tachycardia. After laboratory investigations, a diagnosis of Emery-Dreifuss muscular dystrophy was suspected. Physiotherapy was started, wheel chair was prescribed, and referral to a specialist center was done for appropriate management.ConclusionsEmery-Dreifuss muscular dystrophy is a rare disabling muscular disease which poses a diagnostic challenge. High index of suspicion is paramount for its early diagnoses to prevent orthopedic and cardiac complications. Prompt diagnosis and management is essential to improve on the prognosis of this disease.

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Section: Discussionmentioning

confidence: 91%

“…A team approach involving a neurologist, pulmonologist, cardiologist, orthopedic surgeon, physical therapist, and counsellors ensures quality care. Emphasis is laid on surgical and nonsurgical management of contractures, and pacemaker implantations to prevent sudden death from cardiac complications [21]. …”

Section: Discussionmentioning

confidence: 99%

Occurrence of Emery-Dreifuss muscular dystrophy in a rural setting of Cameroon: a case report and review of the literature

et al. 2017

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“…Thus, after chronic hypercortisolism had been diagnosed and cured, the patient exhibited atypical partial lipodystrophy, idiopathic inflammatory myopathy, and cardiomyopathy with conduction disturbances. Although this variant has not been shown to be pathogenic with in silico approaches, it has been associated with FPLD2 (7), EDMD2 (8), LGMD1B (9), and heart disease (10).…”

Section: Discussionmentioning

confidence: 99%

“…Although unusual, polymyositis has been associated with cardiac involvement, manifested as rhythm disturbances, conduction defects, and heart failure (23). Similarly, laminopathies, like FPLD2 or LGMD1B (9,14), and particularly the R545H variant, have also been related to heart disease (10). Patients with cardiac compromise related to LMNA typically show initial signs of nonspecific rhythm disturbances after age 30 y (24), and they frequently need a…”

Section: Inflammatory Myopathy and Laminopathymentioning

confidence: 99%

Inflammatory myopathy in the context of an unusual overlapping laminopathy

Guillín-Amarelle¹,

Sánchez-Iglesias²,

Varela³

et al. 2018

Archives of Endocrinology and Metabolism

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Summary Laminopathies are genetic disorders associated with alterations in nuclear envelope proteins, known as lamins. The LMNA gene encodes lamins A and C, and LMNA mutations have been linked to diseases involving fat (type 2 familial partial lipodystrophy [FPLD2]), muscle (type 2 Emery–Dreifuss muscular dystrophy [EDMD2], type 1B limb-girdle muscular dystrophy [LGMD1B], and dilated cardiomyopathy), nerves (type 2B1 Charcot–Marie–Tooth disease), and premature aging syndromes. Moreover, overlapping syndromes have been reported. This study aimed to determine the genetic basis of an overlapping syndrome in a patient with heart disease, myopathy, and features of lipodystrophy, combined with severe metabolic syndrome. We evaluated a 54-year-old woman with rheumatoid arthritis, chronic hypercortisolism (endogenous and exogenous), and a history of cured adrenal Cushing syndrome. The patient presented with a complex disorder, including metabolic syndrome associated with mild partial lipodystrophy (Köbberling-like); mild hypertrophic cardiomyopathy, with Wolff–Parkinson– White syndrome and atrial fibrillation; and limb-girdle inflammatory myopathy. Mutational analysis of the LMNA gene showed a heterozygous c.1634G>A (p.R545H) variant in exon 10 of LMNA . This variant has previously been independently associated with FPLD2, EDMD2, LGMD1B, and heart disease. We describe a new, LMNA -associated, complex overlapping syndrome in which fat, muscle, and cardiac disturbances are related to a p.R545H variant.

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“…All LMNA based muscle diseases have cardiac muscle defects. [15][16][17][18] The muscle-specific degeneration observed in the case of muscle diseases can be explained by the mechanical hypothesis; certain lamin mutations cause nuclei to lose their ability to resist mechanical strain, which in turn leads to nuclear rupture, cell death and tissue deterioration. Mechanically stressed tissues are particularly susceptible as they are constantly under strain, and therefore damage is initially observed in these cells.…”

Section: Introductionmentioning

confidence: 99%

Global transcriptional changes caused by an EDMD mutation correlate to tissue specific disease phenotypes inC. elegans

Zuela

Dorfman

Gruenbaum

2016

Nucleus

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There are numerous heritable diseases associated with mutations in the LMNA gene. Most of these laminopathic diseases, including several muscular dystrophies, are autosomal dominant and have tissue-specific phenotypes. Our previous studies have shown that the globally expressed EmeryDreifuss muscular dystrophy (EDMD)-linked lamin mutation, L535P, disrupts nuclear mechanical response specifically in muscle nuclei of C. elegans leading to atrophy of the body muscle cells and to reduced motility. Here we used RNA sequencing to analyze the global changes in gene expression caused by the L535P EDMD lamin mutation in order to gain better understanding of disease mechanisms and the correlation between transcription and phenotype. Our results show changes in key genes and biological pathways that can help explain the muscle specific phenotypes. In addition, the differential gene expression between wild-type and L535P mutant animals suggests that the pharynx function in the L535P mutant animals is affected by this lamin mutation. Moreover, these transcriptional changes were then correlated with reduced pharynx activity and abnormal pharynx muscle structure. Understanding disease mechanisms will potentially lead to new therapeutic approaches toward curing EDMD.

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Skeletal Muscle Laminopathies: A Review of Clinical and Molecular Features

Cited by 73 publications

References 83 publications

Occurrence of Emery-Dreifuss muscular dystrophy in a rural setting of Cameroon: a case report and review of the literature

Occurrence of Emery-Dreifuss muscular dystrophy in a rural setting of Cameroon: a case report and review of the literature

Inflammatory myopathy in the context of an unusual overlapping laminopathy

Global transcriptional changes caused by an EDMD mutation correlate to tissue specific disease phenotypes inC. elegans

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