板层状鱼鳞病TGM1基因突变研究

目的 探讨一个板层状鱼鳞病家系转谷氨酰胺酶1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基因所有的外显子及其邻近的剪切点并进行双向直接测序,并对TGM1基因的同源性进行分析.结果 板层状鱼鳞病患者TGM1基因存在异常:外显子3的第504位碱基由胞嘧啶突变为胸腺嘧啶,使第142位氨基酸由精氨酸(R)转变为半胱氨酸(C),即R142C错义突变;外显子7的第1122位碱基由胞嘧啶突变为胸腺嘧啶,使348位氨基酸由精氨酸(R)突变为终止密码(R348X),导致其编码的蛋白缺失了C端的470个氨基酸.其父亲为R142C杂合子,母亲为R348X突变杂合子;R142C错义突变位于TGM1基因保守区域.结论 该板层状鱼鳞病患者存在转谷氨酰胺酶1基因的R142C错义突变和R348X无义突变.

Transglutaminase 1 gene mutations in a family with lamellar ichthyosis

Objective To detect the mutations of transglutaminase 1 (TGM1) gene in a family with lamellar ichthyosis. Methods The genomic DNA was extracted from the proband and his family members. All the encoding exons and adjacent splice sites of TGM1 gene were amplified by PCR. Mutation scanning was carried out via direct bi-directional DNA sequencing. Also the homology of TGM1 was analyzed. Results In the proband, there was a C504T mutation located at codon 142 (R142C) in exon 3 of TGM1 gene, and a nonsense mutation of C1122T located in exon 7, which caused a premature termination of R348X and a defective polypeptide truncated by 470 amino acids in C-terminus. A heterozygote of C504T mutation was carried by the proband's father and a heterozygote of C1122T mutation in the proband's mother. The missense mutation of R142C was found at the conservation region of TGM1 gene. Conclusion The mutations of R142C and R348X in TGM1 gene are present in the patient with lamellar ichthyosis.