title: Fas and Fas ligand gene mutations in Hashimoto's thyroiditis.
abstract: To clarify whether Fas and Fas ligand (FasL) mutations are involved in the pathogenesis of Hashimoto's thyroiditis (HT), we examined the open reading frame of Fas and FasL in 21 cases. Mutations of Fas and FasL genes were detected in 8 (38.1%) and 1 (4.8%) of 21 cases, respectively. All but one of the Fas mutations were frameshift mutations, which affect the cytoplasmic region (death domain) known to be involved in apoptotic signal transduction and thus could be loss-of-function mutations. FasL mutation in one case was a 46-bp deletion from nucleotide 349 to 394, which corresponded to exon 2. Lack of exon 2 results in a frameshift, which generates a stop codon at residue 128. This mutant encodes the protein that contains only a part of the intracellular domain, thus the abnormal protein might not be expressed on the cell surface. The cells with Fas mutations were confined to the mantle zone and the germinal center, as determined by microdissection methods. These findings suggest that the cells with Fas mutations might accumulate in those areas and might be involved in the pathogenesis of Hashimoto's thyroiditis.
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Dong
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takakuwa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takayama
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Luo
authors.forename: Toru
authors.initials: T
authors.lastname: Takano
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Amino
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsuzuka
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Aozasa
mesh_terms: D000368:Aged; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D053222:Fas Ligand Protein; D005260:Female; D016368:Frameshift Mutation; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013954:Thyroglobulin / Q000097:blood; D013961:Thyroid Gland / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000235:genetics* / Q000473:pathology; D019014:fas Receptor / Q000235:genetics*
chemical_list: D017931:DNA Primers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D012313:RNA; D004247:DNA; D013954:Thyroglobulin