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 functional...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-A7, fl/A7）, 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.展开更多
基金Project supported by the National Natural Science Foundation of China(Nos.81050034 and 81500979)the Research Foundation of the Capital Institute of Pediatrics(No.Fangxiang-2014-01)the Beijing Talents Fund(No.2014000021469G228)
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-A7, fl/A7）, 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.
