板层状鱼鳞病一家系TGM1突变基因检测

Transglutaminase 1 gene mutation in a family with lamellar iehthyosis

目的报道1例有近亲背景的板层状鱼鳞病患者及其家系，并检测其转谷氨酰胺酶Ⅰ编码基因TGM1的突变。方法提取板层状鱼鳞病患者及家族成员的基因组DNA，采用PCR扩增TGM1基因所有的15个外显子及其邻近的侧翼序列并进行双向直接测序。结果该板层状鱼鳞病患者TGM1基因第11个外显子的1666位的碱基存在胞嘧啶（C）→胸腺嘧啶（T）突变，使得529位密码子由ACA→ATA，相应氨基酸由苏氨酸（Thr）变为异亮氨酸（Ile）。结论患者转谷氨酰胺酶IThr529Ile基因突变可能导致其发病。其父母基因型均为该突变的杂合子，近亲婚配促进基因的纯合，增加后代患病概率。

Objective To reporta consanguineous family with lamellar ichthyosis and to detect the mutations in transglutaminase 1 （TGM1） gene in this family. Methods Genomic DNA was extracted from the blood samples of a 19-year-old male patient with lamellar ichthyosis, his family members and 100 normal human controls. PCR was carried out to amplify all the encoding sequences （15 exons） and adjacent flanking sequences of TGM1 gene followed by bidirectional sequencing. Results A C1666T mutation in the 11th exon in TGM1 gene, which resulted in the substitution of ACA （threonine） by ATA （isoleucine） at codon 529, was detected in the proband, while both his parents carried the C1666T mutation in heterozygous form, and his sister was a C/C homozygote. None of the 100 normal control individuals carried the mutation in TGMlgene. Conclusions The de novo mutation from ACA （threonine） to ATA （isoleucine） at codon 529, may contribute to the development of lamellar ichthyosis. Consanguineous marriage can increase the risk for lamellar ichthyosis by raising the probability of homozygosis of C 1666T mutation in TGMI gene.