Document Detail


Molecular diagnosis of non-deletion SMA patients using quantitative PCR of SMN exon 7.
MedLine Citation:
PMID:  10732817     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The telomeric survival motor neuron (SMN(T)) gene is a valuable molecular diagnostic tool for childhood-onset spinal muscular atrophy (SMA) as homozygous deletions of SMN(T) exon 7 (delta7SMN(T)) are present in approximately 94% of patients. In this report, we provide the first comprehensive study of 32 unrelated non-deletion SMA patients. Quantitative polymerase chain reaction (PCR) studies established that 90% had two intact copies of SMN(T) exon 7 suggesting that these patients do not have 5q SMA. Once 5q SMA is confirmed, the SMN(T) gene can be screened for subtle mutations. Using single strand conformation analysis, we identified two missense mutations (P245L and Y272C) in exon 6 of the SMN(T) gene of two SMA patients shown to have a single copy of SMN(T) exon 7. Y272 is most likely critical for SMN(T) function as it is a target for recurring mutations and is associated with type I SMA. These results emphasize the need for dosage analysis in the differential diagnosis of 5q SMA in nondeletion patients, consistent with extensive clinical heterogeneity and some genetic heterogeneity in this disease. Homozygosity or heterozygosity for a delta7SMN(T) allele confirms the diagnosis of 5q SMA with greater precision than clinical examination alone.
Authors:
C F Rochette; L C Surh; P N Ray; P E McAndrew; T W Prior; A H Burghes; M Vanasse; L R Simard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurogenetics     Volume:  1     ISSN:  1364-6745     ISO Abbreviation:  Neurogenetics     Publication Date:  1997 Sep 
Date Detail:
Created Date:  2000-04-12     Completed Date:  2000-04-12     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9709714     Medline TA:  Neurogenetics     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  141-7     Citation Subset:  IM    
Affiliation:
Department of Genetics, Hôpital Sainte-Justine, Montréal, Québec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution
Base Sequence
Cyclic AMP Response Element-Binding Protein
DNA / chemistry,  genetics
DNA Mutational Analysis
Exons / genetics*
Family Health
Female
Humans
Male
Muscular Atrophy, Spinal / diagnosis,  genetics*
Mutation
Nerve Tissue Proteins / genetics*
Pedigree
Point Mutation
Polymerase Chain Reaction / methods
Polymorphism, Single-Stranded Conformational
RNA-Binding Proteins
SMN Complex Proteins
Chemical
Reg. No./Substance:
0/Cyclic AMP Response Element-Binding Protein; 0/Nerve Tissue Proteins; 0/RNA-Binding Proteins; 0/SMN Complex Proteins; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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