title: [Perforin gene mutations in patients with acquired severe aplastic anemia].
abstract: This study was aimed to explore whether the perforin gene 1 (PRF1) mutation is the basis of genetic susceptibility to pathogenesis of acquired severe aplastic anemia (SAA). DNA exon2 and exon3 of PRF1 gene in peripheral blood mononuclear cells in 31 SAA patients and 15 normal controls were amplified by PCR; the sequencing was performed by using ABI pRISM 373OXL sequencer; the mutation loci were sought through checking sequences with GenBank-reported sequences; after the mutation sequences were found, those were cloned into M13 phage vector, then the corresponding sequences of gained 2 chromosomes were sequenced respectively to determine the distribution of different mutations on chromosomes. The results showed that (1) one homozygous mutation (822 C > T, synonymous mutation) and one heterozygous mutation (907 G > A, methionine 303 valine) were found in PRF1 coding region of 2 SAA patients. These mutations were not detected in normal controls. (2) 1 SNP (rs885822) in the coding region was detected in SAA patients and controls, and the heterozygosity rate between the 2 groups was different (p < 0.05). It is concluded that perforin gene mutation may be one risk factor in the aberrant proliferation and activation of cytotoxic T cells in pathogenesis of a part of patients with aplastic anemia.
authors.affiliation: Department of Hematoloy and Oncology, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.forename: Wen
authors.initials: W
authors.lastname: Qu
authors.forename: Hua-Quan
authors.initials: HQ
authors.lastname: Wang
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Xing
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Wu
authors.forename: Jin
authors.initials: J
authors.lastname: Guan
authors.forename: Guo-Jin
authors.initials: GJ
authors.lastname: Wang
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.forename: Er-Bao
authors.initials: EB
authors.lastname: Ruan
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Zong-Hong
authors.initials: ZH
authors.lastname: Shao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin