Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although defects in the gene encoding the enzyme cytosolic copper/zinc superoxide dismutase (SOD1) have been reported in 20% of familial amyotrophic lateral sclerosis (ALS) patients, the etiology of the remaining familial cases and the more common sporadic form of the disease remains unknown. Recently, deletions of the neuronal apoptosis inhibitory protein gene NAIP, of the survival motor neuron gene SMN, and of a further cDNA fragment, XS2G3, have been reported in childhood-onset proximal spinal muscular atrophy (SMA), another disorder with pathology restricted to the motor system. We have therefore investigated the possibility of alterations in SMN and NAIP in 154 patients with ALS (135 sporadic cases, 17 familial cases). None of these patients revealed mutations in SMN by single-strand conformation polymorphism analysis. A single patient revealed a partial deletion of NAIP, with a homozygous absence of NAIP exon 5. While it is possible that this individual is one of the rare carriers of SMA who show NAIP deletions, a further explanation is that the NAIP deletion is in some way contributing to the ALS phenotype in this individual.
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PMID:Analysis of chromosome 5q13 genes in amyotrophic lateral sclerosis: homozygous NAIP deletion in a sporadic case. 865 52

Motor neuron diseases in humans, which include amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies (SMAs), are characterized by motorneuron loss and chromatolysis in some or many remaining cells of the anterior horn of the spinal cord. Motorneurons are filled with phosphorylated neurofilaments, and ubiquitinated filamentous and granular inclusions which conform Lewy-like bodies in ALS patients. In addition, axonal balloonings filled with phosphorylated neurofilaments are usually observed in ALS patients with predominant signs of spinal motor neuron deficits and rapid clinical course. SMAs also occur in other species. Loss of motorneurons and chromatolytic cells filled with phosphorylated neurofilaments are the main pathologic findings in the ventral horn. In both humans and animals, loss of synaptic afferents is found in chromatolytic cells but not in normally-appearing motorneurons, thus suggesting that loss of synapses is a later event in motor neuron disease. These morphological features, together with the lack of c-Jun/AP-1 immunostaining and lack of staining with the method of in situ labelling of nuclear DNA fragmentation of dying cells, are different from those found during the process of naturally occurring (programmed) cell death in normal development. Although deletions in the SMN and NAIP genes located in 5q are found in patients with SMA, the cell death programme in SMA should not be considered as a mere persistence or reactivation of naturally occurring (programmed) cell death during normal development.
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PMID:[Motor neuron diseases: a type of programmed cell death?]. 904 76

Amyotrophic lateral sclerosis (ALS) is found in a familial form in around 5-10% of cases. Of these familial cases around 20% are associated with mutations of SOD-1. The genetic basis of the disease in the remaining familial cases, and genetic risk factors in sporadic cases, are unknown. Recently, the common forms of spinal muscular atrophy (SMA) have been associated with mutations of the SMN and NAIP genes on chromosome 5, in the region q11.2-13.3. Some patients with both familial and sporadic motor neuron disease show only lower motor neuron signs, in common with SMA patients, and families containing individuals with phenotypes of both childhood SMA and adult motor neuron disease have been reported. We therefore examined the SMA locus as a candidate for ALS, in 54 patients with sporadic motor neuron disease, and 10 single-generation familial patients (with no evidence of SOD-1 mutations), and in a single patient with Brown-Vialetto-Van Laere syndrome. No mutations of the SMN or NAIP genes were detected. The difficulties of classification of lower motor neuron presentations of motor neuron diseases are discussed. The demonstration that mutations diagnostic of SMA are not found in ALS patients helps distinguish these conditions.
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PMID:The relationship of spinal muscular atrophy to motor neuron disease: investigation of SMN and NAIP gene deletions in sporadic and familial ALS. 907 29

About 10 p. cent of amyotrophic lateral sclerosis (ALS) cases are familial. Most of the familial ALS (FALS) cases are clinically homogeneous. Among these families, autosomal dominant, X-linked or autosomal recessive transmission can be observed. Most of the causal mutations have been observed in the SOD1 gene. To date, more than one hundred different mutations have been described, but it remains unclear whether the mutation is always responsible for the phenotype. Penetrance of the mutation depends on age, with almost 90 p. 100 of penetrance at age 70 years. There is no anticipation. Worldwide, the most frequent mutation is A4V with dominant transmission, responsible for a severe, rapid form of the disease. The second most frequent mutation is D90A which is generally transmitted recessively, predominantly in the Scandinavian countries. The phenotype is characterized by a long lasting course (mean: 11 years). Other causal mutations have been described in the Alsine, Apex, NF-H and NAIP genes. Other genes can be considered as risk factors, like SMN2, APO E4, APEX, Dynactine, P-450 D6. Presymptomatic testing for FALS seems difficult because little information can be given to the patient regarding the responsibility of the mutation in the disease, age of onset, and disease trends. The same precautions as for Huntington's disease are needed. Genetic investigations can contribute to better understanding of the pathophysiology of ALS. Other causal genes in the 90 p. 100 of FALS without SOD1 mutation and eventually in the sporadic ALS cases may be disclosed. Genetic investigations also determine the precise role of a given SOD1 mutation because of the large number of potential SOD1 mutations, the variability of the transmission mode and the non-exceptional absence of proven causality for ALS.
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PMID:[Where is the role of the genetic investigations in amyotrophic lateral sclerosis?]. 1712 95