Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A sporadic case of the rare and most severe neonatal form of nemaline myopathy is reported. Intrauterine manifestation included reduced fetal movements and breech position with a normal amount of amniotic fluid. After delivery by Caesarian section at 34 weeks of gestation the infant boy, who was not asphyctic, failed to establish spontaneous breathing and required immediate intubation and ventilation. Marked muscular hypotonia and weakness persisted and reflexes remained absent. Hip dislocation, joint contractures, absent palmar creases, prominent lateral palatal ridges and cryptorchidism were interpreted as consequent to prenatal paralysis. The boy died after 5 h due to hyaline membrane disease and meconium aspiration. At autopsy the skeletal muscles were found to be hypoplastic. The muscle fibres contained numerous rods, a typical finding of nemaline myopathy. Nemaline myopathy should be considered in fetuses and newborns with multiple joint contractures, severe muscular weakness and respiratory insufficiency.
 ...
PMID:Neonatal nemaline myopathy presenting with multiple joint contractures. 241 8

Four rare forms of inherited myopathy are reviewed. Nemaline myopathy shows certain well-defined clinical characteristics and rodlike structures derived from Z-band protein accumulate within the muscle fibers. Myotubular or centronuclear myopathy presents usually with infantile hypotonia and the majority of the muscle fibers demonstrate central nuclei surrounded by perinuclear halos, developmental arrest may well be followed by perinuclear degeneration. Glycogen storage disease due to acid maltase deficienty is now recognized as an occasional cause of late-onset myopathy. An unusual case of myopathy due to lipid storage in Type I muscle fibers is described.
 ...
PMID:Some rare congenital and metabolic myopathies. 529 16

Nemaline myopathy (NM) is a rare autosomal dominant skeletal muscle myopathy characterized by severe muscle weakness and the subsequent appearance of nemaline rods within the muscle fibers. Recently, a missense mutation inTPM3, which encodes the slow skeletal alpha-tropomyosin (alphaTm), was linked to NM in a large kindred with an autosomal-dominant, childhood-onset form of the disease. We used adenoviral gene transfer to fully differentiated rat adult myocytes in vitro to determine the effects of NM mutant human alphaTm expression on striated muscle sarcomeric structure and contractile function. The mutant alphaTm was expressed and incorporated correctly into sarcomeres of adult muscle cells. The primary defect caused by expression of the mutant alphaTm was a decrease in the sensitivity of contraction to activating Ca(2+), which could help explain the hypotonia seen in NM. Interestingly, NM mutant alphaTm expression did not directly result in nemaline rod formation, which suggests that rod formation is secondary to contractile dysfunction and that load-dependent processes are likely involved in nemaline rod formation in vivo.
 ...
PMID:A nemaline myopathy mutation in alpha-tropomyosin causes defective regulation of striated muscle force production. 1058 21

Nemaline myopathy (NM) is the most common of several congenital myopathies that present with skeletal muscle weakness and hypotonia. It is clinically heterogeneous and the diagnosis is confirmed by identification of nemaline bodies in affected muscles. The skeletal muscle alpha-actin gene (ACTA1) is one of five genes for thin filament proteins identified so far as responsible for different forms of NM. We have screened the ACTA1 gene in a cohort of 109 unrelated patients with NM. Here, we describe clinical and pathological features associated with 29 ACTA1 mutations found in 38 individuals from 28 families. Although ACTA1 mutations cause a remarkably heterogeneous range of phenotypes, they were preferentially associated with severe clinical presentations (p < 0.0001). Most pathogenic ACTA1 mutations were missense changes with two instances of single base pair deletions. Most patients with ACTA1 mutations had no prior family history of neuromuscular disease (24/28). One severe case, caused by compound heterozygous recessive ACTA1 mutations, demonstrated increased alpha-cardiac actin expression, suggesting that cardiac actin might partially compensate for ACTA1 abnormalities in the fetal/neonatal period. This cohort also includes the first instance of an ACTA1 mutation manifesting with adult-onset disease and two pedigrees exhibiting potential incomplete penetrance. Overall, ACTA1 mutations are a common cause of NM, accounting for more than half of severe cases and 26% of all NM cases in this series.
 ...
PMID:Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin gene mutations. 1523 5

Nemaline myopathy has been associated with mutations in five different genes, which all encode protein components of the sarcomeric thin filaments. We report follow-up studies in two children with mutations not previously described in skeletal muscle alpha-actin (ACTA1). Case 1 was a male patient who after birth suffered from pronounced muscle weakness and hypotonia. Muscle biopsy showed small fibers with numerous rods. He failed to achieve any motor milestones. At the age of 17 he required 24 h ventilator support. He could not lift his arms against gravity, but he could use his hands to control his electric wheelchair. The muscle biopsy showed marked replacement of muscle tissue by fat and connective tissue. Only few fibers showed nemaline rods. He had a de novo, heterozygous mutation, G268D in ACTA1. Case 2 was a female patient with feeding difficulties and mild hypotonia in the neonatal period. Muscle biopsy showed hypoplastic muscle fibers and numerous rods. At 11 years of age she walked and moved unhindered and could run fairly well. She had a de novo, heterozygous mutation, K373E, in ACTA1. These two patients illustrate the marked variability in the clinical features of nemaline myopathy in spite of similar muscle pathology in early childhood. The severe muscle atrophy with replacement of fat and connective tissue in case 1 demonstrates the progressive nature of nemaline myopathy in some cases. The described two mutations add to the previously reported mutations in ACTA1 associated with nemaline myopathy.
 ...
PMID:Follow-up of nemaline myopathy in two patients with novel mutations in the skeletal muscle alpha-actin gene (ACTA1). 1533 87

Nemaline myopathy is a neuromuscular disorder, characterized by muscle weakness and hypotonia and is, in 20% of the cases, caused by mutations in the gene encoding alpha-skeletal muscle actin, ACTA1. It is a heterogeneous disease with various clinical phenotypes and severities. In patients the ultrastructure of muscle cells is often disturbed by nemaline rods and it is thought this is the cause for muscle weakness. To search for possible defects during muscle cell differentiation we expressed alpha-actin mutants in myoblasts and allowed these cells to differentiate into myotubes. Surprisingly, we observed two striking new phenotypes in differentiating myoblasts: rounding up of cells and bleb formation, two features reminiscent of apoptosis. Indeed expression of these mutants induced cell death with apoptotic features in muscle cell culture, using AIF and endonuclease G, in a caspase-independent but calpain-dependent pathway. This is the first report on a common cellular defect induced by NM causing actin mutants, independent of their biochemical phenotypes or rod and aggregate formation capacity. These data suggest that lack of type II fibers or atrophy observed in nemaline myopathy patients may be also due to an increased number of dying muscle cells.
 ...
PMID:alpha-Skeletal muscle actin nemaline myopathy mutants cause cell death in cultured muscle cells. 1939 68

Nemaline myopathy is a heterogenous form of congenital myopathy characterised by a variable spectrum of clinical features, predominated in the severe form by profound muscle hypotonia and weakness accompanied by respiratory insufficiency. The clinical variability, with differing age of onset and severity of symptoms makes the diagnosis of nemaline myopathy difficult in some cases. Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle. We describe the severe form of nemaline myopathy diagnosed in two brothers who died at the age of 12 days and 9 months, due to respiratory insufficiency caused by severe muscle weakness. Polyhydramnios and weakness of foetal movements in the IIIrd trimester of pregnancy, as well as variable clinical severity were noted in both cases. Microscopically visible significant immaturity of muscle fibers was found in the skeletal muscle biopsy performed in one of the brothers. The diagnosis of nemaline myopathy was confirmed by the presence of nemaline bodies (rods) in sections stained using the Gomori trichrome method. Molecular studies of DNA isolated from blood leucocytes showed no mutation in the ACTA1 or the TPM3 genes. Linkage analysis with polymorphic markers did not rule out linkage to part of the NEB gene locus. Results of the clinical evaluation and the investigations performed in the family members confirm that it is essential to consider congenital myopathies in the differential diagnosis of neonatal and infantile hypotonia with respiratory insufficiency. Molecular verification of the clinical diagnosis is also important for genetic counselling of the families.
 ...
PMID:[Nemaline myopathy as a cause of neonatal hypotonia - with emphasis on personal experiences. Report of a family with two brothers affected]. 1964 53

Nemaline myopathy (NM) is a congenital disease that leads to hypotonia and feeding difficulties in neonates. Some cases have a more benign course, with skeletal abnormalities later in life. We analyzed a series of eight patients with NM obtained from a retrospective analysis of 4300 muscle biopsies. Patients were classified as having the typical form in five cases, intermediate form in two cases and severe form in one case. Histochemical analysis showed mixed rods distribution in all cases and predominance of type I fibers in five cases. Immunohistochemical analysis showed abnormal nebulin expression in all patients (four heterogeneous and four absent), homogeneous desmin expression in four cases, strongly positive in three and absent in one, fast myosin expression in a mosaic pattern in six cases and absent in two cases. There was no specific relation between these protein expression patterns and the clinical forms of NM.
 ...
PMID:Nemaline myopathy: clinical, histochemical and immunohistochemical features. 1983 23

Nemaline myopathy is a congenital nonprogressive skeletal muscle disorder with a characteristic rod body formation in the skeletal muscle fibers. Cardiac involvement in nemaline myopathy is rare, although both dilated and hypertrophic cardiomyopathy have been reported. We describe an infant diagnosed with hypertrophic cardiomyopathy and hypotonia on the first day of life. Muscle biopsy confirmed nemaline myopathy at 3 weeks of age. The diagnosis of nemaline myopathy precluded consideration of heart transplantation, thus shifting the focus to comfort care. This is the earliest presentation of hypertrophic cardiomyopathy reported in the literature in the setting of nemaline myopathy. The approach to determining an etiology for hypertrophic cardiomyopathy in an infant is reviewed.
 ...
PMID:Hypertrophic cardiomyopathy in a neonate associated with nemaline myopathy. 2206 14

Nemaline myopathy is one of the most common and severe non-dystrophic muscle diseases of childhood. Patients typically present in infancy with hypotonia, weakness, delayed motor development, and bulbar and respiratory difficulties. Mutations in six different genes are associated with nemaline myopathy, with nebulin mutations being the most common. No treatments or disease-modifying therapies have been identified for this disease. One of the major barriers to treatment development is the lack of models amenable to rapid and coordinated testing of potential therapeutic strategies. To overcome this barrier, we have characterized the first zebrafish model of nemaline myopathy. This model, termed neb, harbors a recessive mutation in the nebulin gene that results in decreased Nebulin protein levels, a severe motor phenotype and premature lethality. In addition to impaired motor function, neb zebrafish exhibit many of the features associated with human nemaline myopathy. These include impaired force generation, altered thin filament length and the presence of specific histopathological changes, including the formation of nemaline bodies. In summary, neb zebrafish mirror the genetic, clinical and pathological aspects of nemaline myopathy due to NEB mutation, and thus are an excellent model for future therapy development for this devastating disorder.
 ...
PMID:Neb: a zebrafish model of nemaline myopathy due to nebulin mutation. 2215 74


1 2 3 Next >>