Association between SMN2 methylation and disease severity in Chinese children with spinal muscular atrophy

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• 作者：Yan-yan Cao ; Yu-jin Qu ; Sheng-xi He ; Yan Li…
• 关键词：CpG island ; Methylation ; Survival motor neuron 2 (SMN2) ; Spinal muscular atrophy
• 刊名：Journal of Zhejiang University SCIENCE B
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：17
• 期：1
• 页码：76-82
• 全文大小：737 KB
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• 作者单位：Yan-yan Cao (1)
  Yu-jin Qu (1)
  Sheng-xi He (1)
  Yan Li (1)
  Jin-li Bai (1)
  Yu-wei Jin (1)
  Hong Wang (1)
  Fang Song (1)
  
  1. Department of Medical Genetics, Capital Institute of Pediatrics, Beijing, 100020, China
  
• 刊物主题：Biomedicine general;
• 出版者：Springer Berlin Heidelberg
• ISSN：1862-1783

文摘

The homozygous loss of the survival motor neuron 1 (SMN1) gene is the primary cause of spinal muscular atrophy (SMA), a neuromuscular degenerative disease. A genetically similar gene, SMN2, which is not functionally equivalent in all SMA patients, modifies the clinical SMA phenotypes. We analyzed the methylation levels of 4 CpG islands (CGIs) in SMN2 in 35 Chinese children with SMA by MassARRAY. We found that three CpG units located in CGI 1 (nucleotides (nt) −871, −735) and CGI 4 (nt +999) are significantly hypomethylated in SMA type III compared with type I or II children after receiving Bonferroni correction. In addition to the differentially methylated CpG unit of nt −871, the methylation level of the nt −290/−288/−285 unit was negatively correlated with the expression of SMN2 full-length transcripts (SMN2-fl). In addition, the methylation level at nt +938 was inversely proportional to the ratio of SMN2-fl and lacking exon 7 transcripts (SMN2-Δ7, fl/Δ7), and was not associated with the SMN2 transcript levels. Thus, we can conclude that SMN2 methylation may regulate the SMA disease phenotype by modulating its transcription.