title: ACTN4 gene mutations and single nucleotide polymorphisms in idiopathic focal segmental glomerulosclerosis.
abstract: OBJECTIVE
  To investigate the association between mutations or single nucleotide polymorphisms (SNPs) of the gene ACTN4 in Chinese patients with idiopathic focal segmental glomerulosclerosis (FSGS).
  
  
  METHODS
  Genomic DNA of 82 Chinese idiopathic FSGS patients and 70 healthy people were used to analyze ACTN4 gene mutations by polymerase chain reaction, direct sequencing and GenBank matching. Hair follicle DNA of novel mutated patients' parents were sequenced and alpha-actinin-4 expression in patients' kidney was examined by immunofluorescence. For SNPs, after the Hardy-Weinberg equilibrium test, allele association and the frequencies of genotypes were analyzed, followed by association analysis between genotypes and clinical diagnosis.
  
  
  RESULTS
  We found a heterozygous candidate mutation 184T>A (S62T) in 1 patient and a 5' UTR candidate mutation 1-34C>T in another patient. Both patients had non-nephrotic syndrome FSGS with reduced kidney alpha-actinin-4 expression. Promoter activity analysis suggests that the 1-34C>T candidate mutation may affect the transcriptional regulation of ACTN4 gene. Additionally, 6 novel silent variants and 2 novel SNPs were also found in this study. Novel SNP 484 + 87C>G had a significant association with the level of urine protein excretion in these idiopathic FSGS patients.
  
  
  CONCLUSIONS
  Our data suggest that mutations and SNP of ACTN4 gene may contribute to be associated with Chinese idiopathic FSGS.
authors.affiliation: Department of Nephrology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Shengchuan
authors.initials: S
authors.lastname: Dai
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Pan
authors.forename: Xiaonong
authors.initials: X
authors.lastname: Chen
authors.forename: Weiming
authors.initials: W
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.forename: Qi
authors.initials: Q
authors.lastname: Feng
authors.forename: John Cijiang
authors.initials: JC
authors.lastname: He
authors.forename: Bin
authors.initials: B
authors.lastname: Han
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000185:Actinin / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: D020121:5' Untranslated Regions; C111453:ACTN4 protein, human; D000185:Actinin