Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused
by mutations in the SMN1 gene. The SMN2 gene is highly homologous to SMN1 and has been reported to be correlated with severity of the disease. The clinical
presentation of SMA varies from severe to mild, with three clinical subtypes (type
I, type II, and type III) that are assigned according to age of onset and severity
of the disease. Here, we aim to investigate the potential association between the
number of copies of SMN2 and the deletion in the NAIP gene with the clinical severity of SMA in patients of Malaysian origin. Forty-two
SMA patients (14 of type I, 20 type II, and 8 type III) carrying deletions of the
SMN1 gene were enrolled in this study. SMN2 copy number was determined by fluorescence-based quantitative polymerase chain reaction
assay. Twenty-nine percent of type I patients carried one copy of SMN2, while the remaining 71% carried two copies. Among the type II and type III SMA patients,
29% of cases carried two copies of the gene, while 71% carried three or four copies
of SMN2. Deletion analysis of NAIP showed that 50% of type I SMA patients had a homozygous deletion of exon 5 of this
gene and that only 10% of type II SMA cases carried a homozygous deletion, while all
type III patients carried intact copies of the NAIP gene. We conclude that there exists a close relationship between SMN2 copy number and SMA disease severity, suggesting that the determination of SMN2 copy number may be a good predictor of SMA disease type. Furthermore, NAIP gene deletion was found to be associated with SMA severity. In conclusion, combining
the analysis of deletion of NAIP with the assessment of SMN2 copy number increases the value of this tool in predicting the severity of SMA.
Keywords
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Article info
Publication history
Published online: October 08, 2008
Accepted:
August 22,
2008
Received in revised form:
August 4,
2008
Received:
April 16,
2008
Identification
Copyright
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
