title: Association between SMN2 methylation and disease severity in Chinese children with spinal muscular atrophy.
abstract: 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.
authors.affiliation: Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Cao
authors.affiliation: Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Yu-jin
authors.initials: YJ
authors.lastname: Qu
authors.affiliation: Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Sheng-xi
authors.initials: SX
authors.lastname: He
authors.affiliation: Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Jin-Ll
authors.initials: JL
authors.lastname: Bai
authors.affiliation: Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Yu-wei
authors.initials: YW
authors.lastname: Jin
authors.affiliation: Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Song
mesh_terms: D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D018570:Risk Assessment; D012720:Severity of Illness Index; D014897:Spinal Muscular Atrophies of Childhood / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics
chemical_list: D005819:Genetic Markers; C526477:SMN2 protein, human; D055540:Survival of Motor Neuron 2 Protein
keywords: CpG island; Methylation; Spinal muscular atrophy; Survival motor neuron 2 (SMN2)