Phenotypic Study in 40 Patients With Dysferlin Gene Mutations

Nguyen, Karine; Bassez, Guillaume; Krahn, Martin; Bernard, R.; Laforêt, Pascal; Labelle, Véronique; Urtizberea, Jon Andoni; Figarella‐Branger, Dominique; Romero, Norma B.; Attarian, Shahram; Pouget, Jean; Lévy, Nicolas; Eymard, B.

doi:10.1001/archneur.64.8.1176

Cited by 242 publications

(263 citation statements)

References 24 publications

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“…Different from other limb girdle muscular dystrophies, subacute presentation may occur in about 25% of the patients. It may simulate both clinically and histologically inflammatory myopathies such as polymyositis 38 , as observed on a muscle biopsy of a 16 years old dysferlin-negative female patient ( Figure 2C). …”

Section: Dysferlinopathy (Lgmd2b)mentioning

confidence: 87%

“…Rare patients may present predominant anterior compartment distal weakness 39 . Besides that, there are oligo symptomatic patients with creatine kinase increase 38 . Usually, there is lower limb weakness that, after a period of about 6 years, is followed by upper limb weakness, but this interval may vary from 1 to 16 years 35 .…”

Section: Dysferlinopathy (Lgmd2b)mentioning

confidence: 99%

“…Some dysferlinopathy patients present predominant distal weakness, others proximal and distal weakness 38 . Rare patients may present predominant anterior compartment distal weakness 39 .…”

Section: Dysferlinopathy (Lgmd2b)mentioning

confidence: 99%

“…Phenotypic diagnosis is usually suggested through complete or partial 38 dysferlin deficiency with commercially available antibodies on muscle biopsy, as observed on a 33 years old female patient muscle biopsy ( Figures 3A and 3B). Dysferlin deficiency may also be detected through peripheral monocytes Western blot 38,41 .…”

Section: Dysferlinopathy (Lgmd2b)mentioning

confidence: 99%

“…Dysferlin deficiency may also be detected through peripheral monocytes Western blot 38,41 . Genotypic diagnosis is confirmed through dysferlin gene sequencing 38,41 . Dysferlin is a protein that anchors on the sarcoplasmic membrane and it is necessary to repair membrane microlesions 42 ( Figure 4).…”

Section: Dysferlinopathy (Lgmd2b)mentioning

confidence: 99%

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Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?

Cotta¹,

Carvalho²,

da-Cunha-Júnior³

et al. 2014

Arq. Neuro-Psiquiatr.

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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.Keywords: muscular dystrophies, ultrasonography, biopsy, magnetic resonance imaging, neuromuscular diseases. RESUMOAs distrofias musculares progressivas cintura-membros são desordens neuromusculares hereditárias autossômicas heterogêneas. Elas produzem alterações distróficas à biópsia muscular e estão associadas a mutações em diversos genes envolvidos na estrutura e função muscular. Fluxograma diagnóstico, fotos, tabelas e diagramas ilustrados dos aspectos clínicos, laboratoriais e de imagem são apresentados para o diagnóstico diferencial de distrofias musculares cintura-membros autossômicas recessivas comuns, diagnosticadas atualmente em um centro de referência no Brasil. Exames de imagem pré-operatórios direcionam o local da biópsia muscular. O padrão de envolvimento muscular difere de acordo com o subtipo de distrofia muscular cintura-membros. A substituição fibroadiposa do tecido muscular é mais acentuada no compartimento posterior da coxa na calpainopatia e proteinopatia relacionada à fukutina; anterior da coxa na sarcoglicanopatia; difusa na coxa na disferlinopatia e teletoninopatia. O diagnóstico diferencial preciso das distrofias musculares cintura-membros é importante para o aconselhamento genético, orientação prognóstica, tratamento cardíaco e respiratório. Além disso poderá, no futuro, provavelmente, propiciar terapias gênicas específicas para cada subtipo.Palavras-chave: distrofias musculares, ultrassonografia, biópsia, imagem por ressonância magnética, doenças neuromusculares.

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Section: Dysferlinopathy (Lgmd2b)mentioning

confidence: 87%

Section: Dysferlinopathy (Lgmd2b)mentioning

confidence: 99%

“…Some dysferlinopathy patients present predominant distal weakness, others proximal and distal weakness 38 . Rare patients may present predominant anterior compartment distal weakness 39 .…”

Section: Dysferlinopathy (Lgmd2b)mentioning

confidence: 99%

Section: Dysferlinopathy (Lgmd2b)mentioning

confidence: 99%

Section: Dysferlinopathy (Lgmd2b)mentioning

confidence: 99%

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Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?

Cotta¹,

Carvalho²,

da-Cunha-Júnior³

et al. 2014

Arq. Neuro-Psiquiatr.

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Molecular Genetics of Limb‐Girdle Muscular Dystrophies

Filosto

Scarpelli

Padovani

2015

Encyclopedia of Life Sciences

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The limb‐girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous neuromuscular disorders caused by specific protein defects in muscle fibres and characterised by predominant weakness and wasting in proximal limb and axial muscles. Most of these diseases present with wide clinical heterogeneity and the limb‐girdle phenotype should be regarded as one of the possible phenotypic expressions of a specific protein defect. Therefore, a precise clinical evaluation is often difficult, and an appropriate diagnostic approach using clinical, pathological, biochemical and genetic resources is essential to achieve the correct diagnosis. The current classification of LGMDs is based on inheritance pattern. Dominant forms are classified as type 1 (LGMD1), whereas the recessive forms are classified as type 2 (LGMD2). A progressive alphabetical letter identifies the different involved genes and indicates the order of identification. This review reports a comprehensive update on the genetic bases and the main clinical aspects of these groups of diseases according to protein defect and transmission modality. Key Concepts The limb‐girdle muscular dystrophies (LGMDs) are a heterogeneous group of hereditary neuromuscular disorders caused by specific protein defects in muscle fibres and characterised by predominant weakness and wasting in proximal limb and axial muscles. The current classification of LGMDs is based on inheritance pattern. Dominant forms are classified as type 1 (LGMD1), whereas the recessive forms are classified as type 2 (LGMD2). A progressive alphabetical letter identifies the different involved genes and indicates the order of identification. LGMDs are diseases having wide inter‐ and intra‐familial phenotypic heterogeneity and therefore the limb‐girdle phenotype is often the only one of the possible phenotypic expressions of a specific protein defect. Four recessive LGMDs are caused by mutations in the genes encoding the four members of the skeletal muscle sarcoglycan complex which is a part of the large macromolecular complex of proteins named the dystrophin‐associated protein complex (DAPC) which is thought to have structural functions in providing membrane stability, maintaining the integrity of sarcolemma and in ensuring transduction during muscle contraction. Eight genes have been found to be responsible for an LGMD‐dystroglycanopathy until now. Mutations in these genes reduce dystroglycan glycosylation and cause different phenotypes ranging from mild to dramatic conditions. Limb‐girdle muscular dystrophies should to be considered the mildest expression of the phenotypic spectrum of dystroglycanopathies.

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Plasma Membrane Proteins: Dysferlin, Caveolin, PTRF/Cavin, Integrin α7, and Integrin α9

Straub

Barresi

2013

Muscle Disease

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Phenotypic Study in 40 Patients With Dysferlin Gene Mutations

Cited by 242 publications

References 24 publications

Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?

Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?

Molecular Genetics of Limb‐Girdle Muscular Dystrophies

Plasma Membrane Proteins: Dysferlin, Caveolin, PTRF/Cavin, Integrin α7, and Integrin α9

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