Abstract
Spinal muscular atrophy is an autosomal recessive neurodegenerative disorder with
progressive weakness and atrophy of voluntary muscles. The survival motor neuron gene
(SMN) is present in two highly homologous copies (SMN1 and SMN2) on chromosome 5q13.
Homozygous deletion of exons 7 and 8 of SMN1 is responsible for spinal muscular atrophy.
In spinal muscular atrophy patients, SMN2 partially compensates for the lack of SMN1.
Previously, we reported the relatively high incidence of a large deletion including
the SMN1 region in Japanese spinal muscular atrophy type I patients. In order to further
establish the genetic background of Japanese spinal muscular atrophy type I patients,
we investigated the SMN1/SMN2 ratio in the carriers. In normal individuals, there
is one copy of each gene on the chromosome (the SMN1/SMN2 ratio was 1). Among 15 carriers
(14 parents and one carrier sibling of Japanese type I spinal muscular atrophy patients
with homozygous deletion of exons 7 and 8 of SMN1), we found that the SMN1/SMN2 ratio
was 0.5 or 1 in 11 (73.3%) carriers. The remaining four carriers had an SMN1/SMN2
ratio of 1/3. This finding supports the idea that deletion rather than conversion
is the main genetic event in type I spinal muscular atrophy. In addition, the ratio
of SMN1/SMN2 among Japanese carriers, which was thought to be higher than that of
the Western population, was compatible with the results obtained in Western populations.
For further insight into the characteristic genetic background of spinal muscular
atrophy in Japanese, determination of the gene copy number is essential.
Keywords
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Article info
Publication history
Accepted:
May 28,
2001
Received in revised form:
April 24,
2001
Received:
February 16,
2001
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
