Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q16637 (SMA)
 8,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proximal spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder characterized by degeneration of anterior horn cells in the spinal cord leading to weakness and wasting of voluntary muscles. Here we present the molecular analysis of both SMA candidate genes, the survival motor neuron gene (SMN; exons 7 and 8) and the neuronal apoptosis inhibitory protein gene (NAIP; exons 5, 6 and 13), in 195 patients and 348 parents of SMA families mainly of German origin. The SMN gene is homozygously deleted for both exons 7 and 8 or exon 7 only in 96% of type I SMA, 94% of type II SMA and 82% of type III SMA as well as in 0.3% of SMA parents. The NAIP gene is homozygously deleted in 46% of type I SMA, 17% of type II SMA, 7% of type III SMA and 2% of SMA parents. The frequencies of deletions in patients for both genes, SMN and NAIP, correspond to those for the NAIP gene only. SMA patients of this series who did not show deletions were clinically indistinguishable from deleted patients. In addition to one unaffected mother of a type II SMA patient, we found homozygous deletions of the SMN gene exons 7 and 8 in six further unaffected individuals, all sibs of type II and III patients. These belonged to four families with affected and unaffected sibs who showed identical haplotypes for all SMA flanking markers; therefore, we had regarded these families as chromosome 5 unlinked. All seven unaffected individuals in whom we detected SMA deletions do not show any signs of muscle weakness and are physically inconspicuous. The largest divergence between age at onset of an affected subject and the present age of unaffected deleted sibs is four decades now. The occurrence of SMN deletions in unaffected individuals suggests that other genes or mechanisms may be necessary to produce the SMA phenotype.
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PMID:Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: evidence of homozygous deletions of the SMN gene in unaffected individuals. 859 17

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

Two genes are known to be involved in spinal muscular atrophy (SMA), namely, SMN (survival motor neuron) and NAIP (neuronal apoptosis inhibitory protein). Deletion analysis of these genes has been reported for many ethnic groups. We have extended this analysis to include 15 Arabic patients (11 unrelated cases of type I, which represent practically all of the patients diagnosed within the last 2 years in Kuwait, and 4 type-II cases from a single kinship). Also, 41 healthy relatives (parents and sibs) and 44 control individuals of Arabic origin were analyzed. The homozygous deletions of exons 7 and 8 of the SMN gene were found in all SMA patients studied. Exon 5 of NAIP was homozygously absent in all type-I patients, but was retained in type-II cases. Among members of SMA families, one mother was found to be homozygously deleted for NAIP. All of the control individuals had both normal SMN and NAIP. Our results are in agreement with the general consensus that the incidence of NAIP deletion is higher in the more severe SMA cases. Furthermore, they suggest that SMA type-I chromosomes, with the dual deletion of the SMN and NAIP genes, are more common in Arabs than in patients of other ethnic origin.
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PMID:Deletion analysis of the SMN and NAIP genes in Kuwaiti patients with spinal muscular atrophy. 888 69

Three type III spinal muscular atrophy (SMA) families are described in which the same deletion pattern for SMN gene and flanking loci is apparent in both affected and unaffected siblings. Deletions extending to include the NAIP gene are reported in one sibship. All three individuals in which SMN and/or NAIP deletions were detected showed the same haplotypes for SMA linked microsatellite markers as their affected sibs. The three index cases had a SMA III with early onset (1.5-2 yr) and became chairbound at the age 4, 5 and 20 yr. The three haploidentical sibs were given a clinical severity score. One of them showed no sign of the disease at the age of 4 yr and was considered "unaffected"; a 35-yr-old female, who had no symptoms but showed tongue fasciculations and hand tremor was considered "asymptomatic"; a 34-yr-old female, who had mild muscular weakness since the age of 24, was rated "mild". These observations demonstrate the presence of a continuum of clinical variability within SMA III families. These data suggest that, in these three families at least, the SMA phenotype is caused or influenced by another gene(s) additional to SMN.
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PMID:Discordant clinical outcome in type III spinal muscular atrophy sibships showing the same deletion pattern. 888 55

The search for the SMA defect has culminated in the identification of two candidate 5q13.1 SMA genes, NAIP and SMN both of which are deleted in individuals with SMA. It was postulated that the intact and degenerate versions of NAIP are present in variable and frequently high copy numbers in this region while SMN was proposed to be present in only two copies. In order to assess the copy number of NAIP and SMN we have conducted interphase FISH analysis using NAIP and SMN gene-containing cosmid and plasmid probes. Our results confirm the variability in the number of NAIP signals in non-SMA chromosomes (2-6) and show that SMN is present on average twice per chromosome although in one chromosome 4-5 signals for the SMN-containing cosmid probe were detected. Our analysis reveals that one of four and three of six type I SMA chromosomes had a lower than normal number of NAIP and SMN signals, respectively. In two of six SMA type I chromosomes, complete loss of hybridization signal was observed on one chromosome 5 with our SMN cosmid probe possibly reflecting a large scale deletion. Large scale deletions were not detectable when metaphase chromosomes of an SMA type II and III patient were analyzed.
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PMID:FISH detection of chromosome polymorphism and deletions in the spinal muscular atrophy (SMA) region of 5q13. 906 34

The results of DNA analysis of deletion in exons 7 and 8 of SMN gene, and exon 5 of NAIP gene in 24 SMA-families from Ukraine are presented. Deletions of SMN exons 7 and 8, or 7 were found in 46 (97.9%) of 47 SMA-chromosomes. A homozygous deletion of NAIP exon 5 was demonstrated in 4 (19%) of 21 SMA-families. The authors have demonstrated that in 2 SMA patients with homozygous deletion SMN exon 7 only, the remaining SMN exon 8 was a part of a chimeric CBCD41/SMN gene.
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PMID:[A molecular genetic analysis of spinal muscular atrophy (SMA) in families at high risk from different regions of Ukraine]. 959 48

All three types of autosomal recessive spinal muscular atrophy map to chromosome region 5q13. Recent reports suggest that they are associated with deletions of two adjacent genes: SMN and NAIP. Here we report the first deletion analysis of Bulgarian SMA families. Homozygous deletion of exons 7 and 8 of the SMN gene were found in 85% of our patients, but the NAIP gene (exons 5 and 6) was deleted in only 26% of patients. To our knowledge, these frequencies are some of the lowest reported so far. The NAIP gene was deleted predominantly in severely affected patients (type I), while in the group with milder types SMA only deletions of the SMN gene were detected. Our phenotype-genotype correlation study confirmed that larger deletions are associated with more severe clinical course. The Bulgarian data support the thesis that the telomeric SMN gene could play a major role in determining SMA, while the NAIP or the centromeric SMN copy have a modifying effect on the phenotype.
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PMID:Deletion analysis of Bulgarian SMA families. 963 17

The spinal muscular atrophies (SMA), characterized by motor neuron loss and progressive paralysis, are among the most common autosomal recessive disorders. Recently, two SMA candidate genes, NAIP (neuronal apoptosis inhibitory protein) and survival motor neuron (SMN), were reported and a 131-kb genomic sequence of 5q13.1 encompassing these two genes was determined. Based upon this genomic sequence, the original NAIP cDNA sequence published in 1995 was shown to contain foreign fragments. We therefore conducted an extensive cDNA cloning of NAIP from a human fetal brain library. Our studies confirmed that the cDNA sequence deduced from the 131-kb genomic sequence was the major transcript in the human fetal brain. In addition, a shorter and minor transcript was also newly identified. We thus designated the longer and shorter transcripts as NAIPl and NAIPs, respectively. The cDNA clones for NAIPl and NAIPs should facilitate the functional analysis of the NAIP gene and its association with neuronal apoptosis and SMA.
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PMID:Identification of two distinct transcripts for the neuronal apoptosis inhibitory protein gene. 1054 44

Deletions of the spinal muscular atrophy (SMA)-determining gene, SMN1, NAIP, and a third multicopy gene, BTF2p44tel were investigated in 60 unrelated Turkish SMA patients. SMN1 was deleted for at least exons 7 and 8 in 85% of the Turkish SMA patients. The NAIP gene was deleted in 75 and 33% of type I and type II SMA patients, respectively. Analysis of the 5'end of the BTF2p44tel gene indicated the extension of deletion in 13.3% of the cases, mainly in type I patients. Deletions of the NAIP and BTF2p44tel genes were detected in 1.3 and 3.9% of carrriers, respectively, in Turkish SMA families. Two patients were detected to harbor the hybrid SMN gene, one type II with deletion of the NAIP gene, and one type III without deletion of the NAIP gene.
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PMID:Screening of deletions in SMN, NAIP and BTF2p44 genes in Turkish spinal muscular atrophy patients. 1068 93

Childhood SMAs are common neuromuscular disorders, due to the occurrence of large genomic deletions encompassing the SMN gene and often extending to involve the NAIP gene. Although NAIP deletions are more frequently observed in patients affected by the acute form of the disease, it is not possible to establish an unambiguous correlation between deletion size and clinical severity. We have investigated the effects of gender on the association between NAIP gene deletion and disease severity. NAIP deletions were screened in 197 Italian SMA patients lacking SMN; the results obtained were correlated with disease severity in male and female samples separately. No significant relationship between deletion size and clinical phenotype was observed among male subjects, whereas in females the absence of NAIP was strongly associated with a severe phenotype (p <0.0001). These results provide a possible molecular explanation for the sex-dependent phenotype variation observed in SMA patients.
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PMID:A possible role of NAIP gene deletions in sex-related spinal muscular atrophy phenotype variation. 1073 71


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