Limb–girdle muscular dystrophies

Guglieri, Michela; Straub, Volker; Bushby, K.; Lochmüller, Hanns

doi:10.1097/wco.0b013e32830efdc2

Cited by 106 publications

(72 citation statements)

References 70 publications

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“…Immunostaining performed on muscle biopsy and genetic analysis can define the diagnosis of the LGMD subtypes. 52 In a recent analysis conducted in a large sample of genetically diagnosed LGMD Italian patients, CAV3 mutations represented the 5% of the probands. 53 The first description of an LGMD associated with Cav-3 deficiency was by Minetti et al 54 who reported affected individuals in two unrelated Italian families.…”

Section: Caveolin-3 and Muscle Diseasesmentioning

confidence: 99%

Caveolinopathies: from the biology of caveolin-3 to human diseases

et al. 2009

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Section: Caveolin-3 and Muscle Diseasesmentioning

confidence: 99%

Caveolinopathies: from the biology of caveolin-3 to human diseases

et al. 2009

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“…An important group of muscular dystrophies is limb-girdle muscular dystrophies, which predominantly present with proximal weakness with sparing of the facial and distal muscles, and cardiomyopathy in some subtypes [2]; however even when the disease begins with limb-girdle weakness, additional clinical features lead to consider other myopathic disorders. When limb-girdle weakness is combined with early distal muscle involvement, contractures and cardiac involvement, the phenotype is usually categorized as Emery-Dreifuss muscular dystrophy (EDMD) [3,4].…”

Section: Introductionmentioning

confidence: 99%

Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies

Kayman-Kurekci

Talim

Korkusuz

et al. 2014

Neuromuscular Disorders

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We performed genome-wide homozygosity mapping and mapped a novel myopathic phenotype to chromosomal region 1q25 in a consanguineous family with three affected individuals manifesting proximal and distal weakness and atrophy, rigid spine and contractures of the proximal and distal interphalangeal hand joints. Additionally, cardiomyopathy and respiratory involvement were noted. DNA sequencing of torsinA-interacting protein 1 (TOR1AIP1) gene encoding lamina-associated polypeptide 1B (LAP1B), showed a homozygous c.186delG mutation that causes a frameshift resulting in a premature stop codon (p.E62fsTer25). We observed that expression of LAP1B was absent in the patient skeletal muscle fibres. Ultrastructural examination showed intact sarcomeric organization but alterations of the nuclear envelope including nuclear fragmentation, chromatin bleb formation and naked chromatin. LAP1B is a type-2 integral membrane protein localized in the inner nuclear membrane that binds to both A-and B-type lamins, and is involved in the regulation of torsinA ATPase. Interestingly, luminal domain-like LAP1 (LULL1)-an endoplasmic reticulum-localized partner of torsinA-was overexpressed in the patient's muscle in the absence of LAP1B. Therefore, the findings suggest that LAP1 and LULL1 might have a compensatory effect on each other. This study expands the spectrum of genes associated with nuclear envelopathies and highlights the critical function for LAP1B in striated muscle.

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“…11,20 Variable expressivity was observed in term of age at onset and muscular symptoms. With few exceptions, the adult patients showed the 'canonical' clinical features of LGMD, characterised by slowly progressive proximal muscle weakness in upper and lower limbs, with onset during the fifth decade of life and a relatively benign course.…”

Section: Discussionmentioning

confidence: 99%

A new locus on 3p23–p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H

et al. 2010

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Limb-girdle muscular dystrophies (LGMDs) are a genetically heterogeneous group of neuromuscular disorders with a selective or predominant involvement of shoulder and pelvic girdles. We clinically examined 19 members in a four-generation Italian family with autosomal-dominant LGMD. A total of 11 subjects were affected. Clinical findings showed variable expressivity in terms of age at onset and disease severity. Five subjects presented with a slowly progressive proximal muscle weakness, in both upper and lower limbs, with onset during the fourth-fifth decade of life, which fulfilled the consensus diagnostic criteria for LGMD. Earlier onset of the disease was observed in a group of patients presenting with muscle weakness and/or calf hypertrophy, and/or occasionally high CK and lactate serum levels. Two muscle biopsies showed morphological findings compatible with MD associated with subsarcolemmal accumulation of mitochondria and the presence of multiple mitochondrial DNA deletions. A genome-wide scan performed using microsatellite markers mapped the disease on chromosome 3p23-p25.1 locus in a 25-cM region between markers D3S1263 and D3S3685. The highest two-point LOD score was 3.26 (h¼0) at marker D3S1286 and D3S3613, whereas non-parametric analysis reached a P-value¼0.0004. Four candidate genes within the refined region were analysed but did not reveal any mutations. Our findings further expand the clinical and genetic heterogeneity of LGMDs.

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Limb–girdle muscular dystrophies

Cited by 106 publications

References 70 publications

Caveolinopathies: from the biology of caveolin-3 to human diseases

Caveolinopathies: from the biology of caveolin-3 to human diseases

Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies

A new locus on 3p23–p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H

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