Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LGMD1B is an autosomal dominantly inherited, slowly progressive limb girdle muscular dystrophy, with age-related atrioventricular cardiac conduction disturbances and the absence of early contractures. The disease has been linked to chromosome 1q11-q21. Within this locus another muscular dystrophy, the autosomal dominant form of Emery-Dreifuss muscular dystrophy (AD-EDMD) has recently been mapped and the corresponding gene identified. AD-ADMD is characterized by early contractures of elbows and Achilles tendons and a humero-peroneal distribution of weakness combined with a cardiomyopathy with conduction defects. The disease gene of AD-EDMD is LMNA which encodes lamins A/C, two proteins of the nuclear envelope. In order to identify whether or not LGMD1B and AD-EDMD are allelic disorders, we carried out a search for mutations in the LMNA gene in patients with LGMD1B. For this, PCR/SSCP/sequencing screening was carried out for the 12 exons of LMNA on DNA samples of individuals from three LGMD1B families that were linked to chromo-some 1q11-q21. Mutations were identified in all three LGMD1B families: a missense mutation, a deletion of a codon and a splice donor site mutation, respectively. The three mutations were identified in all affected members of the corresponding families and were absent in 100 unrelated control subjects. The present identification of mutations in the LMNA gene in LGMD1B demonstrates that LGMD1B and AD-EDMD are allelic disorders. Further analysis of phenotype-genotype relationship will help to clarify the variability of the phenotype observed in these two muscular dystrophies.
 ...
PMID:Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). 1081 26

A case of autosomal dominant limb-girdle muscular dystrophy with atrioventricular conduction block (LGMD1B) has been documented. In this family, 13 members, nine males and four females, had cardiac arrhythmia requiring pacemakers. The proband, a 67-year-old male, had longstanding proximal muscle weakness later associated with cardiac arrhythmia but showed neither rigid spine nor joint contracture. His muscle enzymes were within normal range and muscle biopsy showed myopathic changes. Gene analysis of the proband revealed Tyr481His mutation in the exon 8 of lamin A/C (LMNA) gene which is adjacent to the codon mutated in reported cases of familial partial lipodystrophy. This is the first report of muscular dystrophy shown to have a mutation of LMNA in a Japanese family as well as the first case of missense mutation in the exon 8 with LGMD1B phenotype.
 ...
PMID:A missense mutation in the exon 8 of lamin A/C gene in a Japanese case of autosomal dominant limb-girdle muscular dystrophy and cardiac conduction block. 1152 83

Limb girdle muscular dystrophies (LGMDs) are a genetically heterogeneous group of primary myopathies involving progressive weakness and wasting of the muscles in the hip and shoulder girdles, with distal spread to the bulbar or respiratory musculature in rare cases. Depending on the mode of genetic transmission, six autosomal dominant forms (LGMD1A-F, 10-25%) and ten autosomal recessive forms (LGMD2A-J, 75-90%) are currently known. The prevalence of LGMDs is 0.8/100,000. These conditions are caused by mutations in genes encoding for myotilin (5q31, LGMD1A), lamin A/C (1q11-q21.2, LGMD1B), caveolin-3 (3p25, LGMD1C), unknown proteins (7q, LGMD1D, 6q23, LGMD1E, 7q32.1-32.2., LGMD1F), calpain-3 (15q15.1-21.1, LGMD2A), dysferlin (2p13.3-13.1, LGMD2B), gamma-sarcoglycan (13q12, LGMD2C), alpha-sarcoglycan, also known as adhalin (17q12-q21.3, LGMD2D), beta-sarcoglycan (4q12, LGMD2E), delta-sarcoglycan (5q33-q34, LGMD2F), telethonin (17q11-q12, LGMD2G), E3-ubiquitin ligase (9q31-q34.1, LGMD2H), fukutin-related protein (19q13.3, LGMD2I), and titin (2q31, LGMD2J). Cardiac involvement has been described for LGMD1B-E, LGMD2C-G, and LGMD2I. The time of onset varies between early childhood and middle age. There is no male or female preponderance. Disease progression and life expectancy vary widely, even among different members of the same family. The diagnosis is based primarily on DNA analysis. The history, clinical neurological examinations, blood chemistry investigations, electromyography, and muscle biopsy also provide information that is helpful for the diagnosis. No causal therapy is currently available.
 ...
PMID:[Limb girdle muscular dystrophies]. 1531 18

Mutations of the LMNA gene, encoding the nuclear envelope proteins lamins A and C, give rise to Emery-Dreifuss muscular dystrophy and to limb-girdle muscular dystrophy 1B (EDMD and LGMD1B). With one exception, all the reported EDMD and LGMD1B mutations are confined to the first 10 exons of the gene. We report four separate cases, with mutations in the same codon of LMNA exon 11, characterized by remarkable variability of clinical findings, in addition to features not previously reported. One patient had congenital weakness and died in early childhood. In two other patients, severe cardiac problems arose early and, in one of these, cardiac signs preceded by many years the onset of skeletal muscle weakness. The fourth case had a mild and late-onset LGMD1B phenotype. Our cases further expand the clinical spectrum associated with mutations in the LMNA gene and provide new evidence of the role played by the C-terminal domain of lamin A.
 ...
PMID:Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene. 1577 Jun 69

The nuclear envelopathies, more frequently known as laminopathies are a rapidly expanding group of human hereditary diseases caused by mutations of genes that encode proteins of the nuclear envelope. The most frequent and best known form is Emery-Dreifuss muscular dystrophy (EDMD), a skeletal myopathy characterized by progressive muscular weakness, joint contractures, and cardiac disease. EMD gene, encoding emerin, causes the X-linked form of EDMD, while LMNA gene encoding lamins A and C, is responsible for autosomal forms, usually with a dominant transmission. In the last years, the spectrum of conditions has been extraordinarily enlarged, from a congenital muscular dystrophy with severe paralytic or rapidly progressive picture due to de novo mutations in LMNA (L-CMD) to a limb-girdle muscular dystrophy with adult onset and much milder weakness (LGMD1B). LMNA has also been involved in a form of isolated cardiomyopathy associated with cardiac conduction disease and in an axonal form of hereditary neuropathy. Identification of this gene has been reported also in a number of non-neuromuscular disorders including lipodystrophy syndromes and a wide spectrum of premature aging syndromes ranging from mandibuloacral dysplasia to restrictive dermopathy. Mutations in other genes implicated in the processing or maturation of nuclear lamins have also been found. The extraordinary complexity of the molecular and pathophysiological mechanisms of these diseases is still not well known and the occurrence of modifying factors or genes is highly suspected. Identification of new genes and investigation of new therapeutic approaches are in progress.
 ...
PMID:Emery-Dreifuss muscular dystrophy, laminopathies, and other nuclear envelopathies. 2362 60