TY - JOUR
T1 - Analysis of the mRNA transcripts of the survival motor neuron (SMN) gene in the tissue of an SMA fetus and the peripheral blood mononuclear cells of normals, carriers and SMA patients
AU - Jong, Yuh Jyh
AU - Chang, Jan Gowth
AU - Lin, Shuan Pei
AU - Yang, Tzu Yao
AU - Wang, Jyh Chwan
AU - Chang, Chih Peng
AU - Lee, Cheng Chun
AU - Li, Hung
AU - Hsieh-Li, Hsiu Mei
AU - Tsai, Chang Hai
N1 - Funding Information:
This work was supported by the Bureau of Health Promotion and Protection, Department of Health, Executive Yuan, Taiwan, and in part by grants from the National Science Council, Taiwan (NSC 86-2314-B-196-002-M02 and NSC 86-2314-B-037-018). We thank the patients and their families, and the physicians who have contributed to this project. We also thank Dr. Mary Jeanne Buttrey for her suggestions and English correction.
PY - 2000/2/15
Y1 - 2000/2/15
N2 - Spinal muscular atrophy (SMA) is a disorder characterized by degeneration of the anterior horn cells of the spinal cord. The gene most highly associated with SMA is the survival motor neuron (SMN) gene. In this study, we present an analysis of messenger RNA (mRNA) expression of the SMN gene in peripheral blood mononuclear cells in normal subjects, SMA carriers and patients from 20 SMA families. We found at least 6-8 different transcripts of SMN gene formed by alternative splicing involving exons 3, 5 and 7. We compared transcripts from the different types of SMA and found no definite differences in transcript patterns and amounts. Normal subjects with the telomeric SMN (SMN(T)) gene only had variable splicing resulting in several transcripts, the most dominant being a transcript containing all coding regions. However, SMA patients with the centromeric SMN (SMN(C)) gene only had a higher degree of splice variation and tended to show little or no exon 7. These results demonstrate that SMN(T) and SMN(C) genes participate in alternative splicing phenomena. The different splicing patterns support the view that the SMN(T) gene is responsible for SMA disease. We also analyzed the transcripts from several tissues of an SMA fetus who had a homozygous SMN(T) gene deletion. Different splicing patterns were also found in these tissues, and were similar to the splicing pattern of leukocytes. We compared the major transcripts from exons 4 to 8 of both the SMN(T) and SMN(C) genes and found that the relative proportion varied among normal subjects, SMA carriers and patients. This approach could be used as a novel diagnostic method. We suggest that analyzing the mRNA expression of the SMN gene in peripheral blood mononuclear cells offers an apparently reliable technique for separating SMA patients, carriers, and normal individuals. (C) 2000 Elsevier Science B.V.
AB - Spinal muscular atrophy (SMA) is a disorder characterized by degeneration of the anterior horn cells of the spinal cord. The gene most highly associated with SMA is the survival motor neuron (SMN) gene. In this study, we present an analysis of messenger RNA (mRNA) expression of the SMN gene in peripheral blood mononuclear cells in normal subjects, SMA carriers and patients from 20 SMA families. We found at least 6-8 different transcripts of SMN gene formed by alternative splicing involving exons 3, 5 and 7. We compared transcripts from the different types of SMA and found no definite differences in transcript patterns and amounts. Normal subjects with the telomeric SMN (SMN(T)) gene only had variable splicing resulting in several transcripts, the most dominant being a transcript containing all coding regions. However, SMA patients with the centromeric SMN (SMN(C)) gene only had a higher degree of splice variation and tended to show little or no exon 7. These results demonstrate that SMN(T) and SMN(C) genes participate in alternative splicing phenomena. The different splicing patterns support the view that the SMN(T) gene is responsible for SMA disease. We also analyzed the transcripts from several tissues of an SMA fetus who had a homozygous SMN(T) gene deletion. Different splicing patterns were also found in these tissues, and were similar to the splicing pattern of leukocytes. We compared the major transcripts from exons 4 to 8 of both the SMN(T) and SMN(C) genes and found that the relative proportion varied among normal subjects, SMA carriers and patients. This approach could be used as a novel diagnostic method. We suggest that analyzing the mRNA expression of the SMN gene in peripheral blood mononuclear cells offers an apparently reliable technique for separating SMA patients, carriers, and normal individuals. (C) 2000 Elsevier Science B.V.
KW - Alternative splicing
KW - Messenger RNA (mRNA)
KW - SMA carrier
KW - Spinal muscular atrophy (SMA)
KW - Survival motor neuron (SMN) gene
KW - Transcript
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U2 - 10.1016/S0022-510X(99)00325-1
DO - 10.1016/S0022-510X(99)00325-1
M3 - Article
C2 - 10675659
AN - SCOPUS:0034651615
SN - 0022-510X
VL - 173
SP - 147
EP - 153
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 2
ER -