Document Detail

An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA).
MedLine Citation:
PMID:  10679938     Owner:  NLM     Status:  MEDLINE    
Spinal muscular atrophy (SMA) is characterized by degeneration of motor neurons in the spinal cord, causing progressive weakness of the limbs and trunk, followed by muscle atrophy. SMA is one of the most frequent autosomal recessive diseases, with a carrier frequency of 1 in 50 and the most common genetic cause of childhood mortality. The phenotype is extremely variable, and patients have been classified in type I-III SMA based on age at onset and clinical course. All three types of SMA are caused by mutations in the survival motor neuron gene (SMN1). There are two almost identical copies, SMN1 and SMN2, present on chromosome 5q13. Only homozygous absence of SMN1 is responsible for SMA, while homozygous absence of SMN2, found in about 5% of controls, has no clinical phenotype. Ninety-six percent of SMA patients display mutations in SMN1, while 4% are unlinked to 5q13. Of the 5q13-linked SMA patients, 96.4% show homozygous absence of SMN1 exons 7 and 8 or exon 7 only, whereas 3. 6% present a compound heterozygosity with a subtle mutation on one chromosome and a deletion/gene conversion on the other chromosome. Among the 23 different subtle mutations described so far, the Y272C missense mutation is the most frequent one, at 20%. Given this uniform mutation spectrum, direct molecular genetic testing is an easy and rapid analysis for most of the SMA patients. Direct testing of heterozygotes, while not trivial, is compromised by the presence of two SMN1 copies per chromosome in about 4% of individuals. The number of SMN2 copies modulates the SMA phenotype. Nevertheless, it should not be used for prediction of severity of the SMA.
B Wirth
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Human mutation     Volume:  15     ISSN:  1059-7794     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2000  
Date Detail:
Created Date:  2000-05-04     Completed Date:  2000-05-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  228-37     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Wiley-Liss, Inc.
Institute of Human Genetics, Bonn, Germany.
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MeSH Terms
Amino Acid Sequence
Cyclic AMP Response Element-Binding Protein
Genes, Recessive*
Molecular Sequence Data
Muscular Atrophy, Spinal / genetics*
Nerve Tissue Proteins / genetics*
RNA-Binding Proteins
SMN Complex Proteins
Survival of Motor Neuron 1 Protein
Survival of Motor Neuron 2 Protein
Reg. No./Substance:
0/Cyclic AMP Response Element-Binding Protein; 0/Nerve Tissue Proteins; 0/RNA-Binding Proteins; 0/SMN Complex Proteins; 0/SMN1 protein, human; 0/SMN2 protein, human; 0/Survival of Motor Neuron 1 Protein; 0/Survival of Motor Neuron 2 Protein

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