Disease relevance of Muscular Atrophy, Spinal

• Reduction in SMN protein results in Spinal muscular atrophy (SMA), a common neurodegenerative disease [1].
• We now show that overexpression of IL-3 in transgenic mice causes a motor neuron disease with several features of amyotrophic lateral sclerosis and progressive muscular atrophy [2].
• Mutations in the immunoglobulin mu binding protein-2 (Ighmbp2) gene cause motor neuron disease and dilated cardiomyopathy (DCM) in the neuromuscular degeneration (nmd) mouse and spinal muscular atrophy with respiratory distress (SMARD1) in humans [3].
• In an attempt to confirm prior reports of vitamin E deficiency in Werdnig-Hoffmann disease, we assessed vitamin E nutritional status in 11 children and 6 adults with spinal muscular atrophy (SMA) [4].
• We confirmed a mutation of the androgen receptor gene as the cause for Kennedy's disease, also called "X-linked recessive spinal and bulbar muscular atrophy" or "bulbospinal neuronopathy." The mutation is characterized by an increased size of a polymorphic tandem CAG repeat within the first exon of the gene [5].

Psychiatry related information on Muscular Atrophy, Spinal

• Ninety-six children and adolescents with spinal muscular atrophy I-III, aged 6.0-18.11 years, 45 non-affected siblings and 59 healthy, matched controls were examined with one- (CPM/SPM), as well as multi-dimensional intelligence tests (Kaufman-ABC; Wechsler tests) [6].

High impact information on Muscular Atrophy, Spinal

• A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy [7].
• Classic spinal muscular atrophy (SMA) is caused by mutations in the telomeric copy of SMN1 [8].
• Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1 [8].
• Our results show that IGHMBP2 is the second gene found to be defective in spinal muscular atrophy, and indicate that IGHMBP2 and SMN share common functions important for motor neuron maintenance and integrity in mammals [8].
• The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins [9].

Chemical compound and disease context of Muscular Atrophy, Spinal

• Cells from a patient with spinal muscular atrophy, containing low levels of the methyl-binding protein SMN, localized sDMA-containing proteins in the nucleoplasm as a discrete granular pattern [10].
• Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy [11].
• Normal vitamin E status in spinal muscular atrophy [4].
• Hydroxyurea enhances SMN2 gene expression in spinal muscular atrophy cells [12].
• A role for polyproline motifs in the spinal muscular atrophy protein SMN. Profilins bind to and colocalize with smn in nuclear gems [13].

Biological context of Muscular Atrophy, Spinal

• The abrogation of the SF2/ASF-dependent ESE is the basis for inefficient inclusion of exon 7 in SMN2, resulting in the spinal muscular atrophy phenotype [14].
• SMN gene deletions in adult-onset spinal muscular atrophy [15].
• The spinal muscular atrophy disease gene product, SMN: A link between snRNP biogenesis and the Cajal (coiled) body [16].
• Patients with autosomal recessive spinal muscular atrophy (SMA) usually carry a homozygous deletion of exons 7 and 8 of the telomeric survival motor neuron (SMN(T)) gene, although an isolated deletion of SMN(T) exon 8 has never been found [17].
• Single point mutations within the Tudor domain, including a spinal muscular atrophy patient mutation, impair the interaction of SMN with GAR1 [18].

Anatomical context of Muscular Atrophy, Spinal

• Three of the five lines showed progressive muscular atrophy and weakness as well as diffuse nuclear staining and nuclear inclusions consisting of the mutant AR [19].
• The distribution of SMN protein complex in human fetal tissues and its alteration in spinal muscular atrophy [20].
• Expression of the SMN gene, the spinal muscular atrophy determining gene, in the mammalian central nervous system [21].
• Here we show that a 46% reduction of Smn protein levels in the spinal cord of Smn heterozygous mice leads to a marked loss of the cytoplasmic Smn pool and motor neuron degeneration resembling spinal muscular atrophy type 3 [22].
• Deletion or mutation of the SMN1 gene reduces intracellular survival motor neurone protein levels causes spinal muscular atrophy, most likely by interfering with spliceosome assembly [23].

Gene context of Muscular Atrophy, Spinal

• The exon 2b region of the spinal muscular atrophy protein, SMN, is involved in self-association and SIP1 binding [24].
• Characterization of Ighmbp2 in motor neurons and implications for the pathomechanism in a mouse model of human spinal muscular atrophy with respiratory distress type 1 (SMARD1) [25].
• A new mutation in the HEXA gene associated with a spinal muscular atrophy phenotype [26].
• The mouse region syntenic for human spinal muscular atrophy lies within the Lgn1 critical interval and contains multiple copies of Naip exon 5 [27].
• Refined mapping of the GM2 activator protein (GM2A) locus to 5q31.3-q33.1, distal to the spinal muscular atrophy locus [28].

Analytical, diagnostic and therapeutic context of Muscular Atrophy, Spinal

• Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy [29].
• CONCLUSION: The SCO2 mutations should be considered in the differential diagnosis of children with spinal muscular atrophy without mutations in the SMN gene [30].
• The extent of neuropathology in a recently reported disease of Brown Swiss cattle, spinal muscular atrophy (SMA), was investigated with light and electron microscopy [31].
• We used linkage analysis, non-isotope SSCP (single-strand conformation polymorphism) and PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) for prenatal diagnosis of spinal muscular atrophy (SMA) [32].

References