长岛型掌跖角化病:SERPINB7基因突变位点研究

Nagashima-type Palmoplantar Keratoderma: Mutation Analysis of the SERPINB7 Gene

目的报道2例长岛型掌跖角化病,确定其致病基因突变。方法收集患者及其中1例母亲外周血和临床资料,提取基因组DNA,PCR扩增SERPINB7基因8个外显子及其侧翼序列,对扩增产物进行DNA测序以查找基因突变位点。结果 2例患者均存在SERPINB7基因c.796C>T杂合突变伴c.455G>T杂合突变,前者可导致编码蛋白质第266位氨基酸出现终止改变(p.R266*),后者可导致第6外显子第1个核苷酸发生改变,使得该外显子的剪接受体位点消失。例1患者母亲为c.455G>T杂合突变而不伴另一突变。正常对照未见这2种突变。结论 SERPINB7基因的c.796C>T和c.455G>T突变是引起2例患者长岛型掌跖角化病的原因。

Objective In order to report two cases of Nagashima-type palmoplantar keratoderma （NPPK）, and to identify mutations in the SERPINB7 gene. Methods Clinical data were collected from two patients with NPPK and one patient＇s mother. Peripheral blood samples were obtained from the two patients and one patient＇s mother. Genomic DNA was extracted from these blood samples. PCR was performed to amplify 8 exons and their flanking sequences of the SERPINB7 gene followed by DNA sequencing. Results Heterozygous mutation c.796C〉T and c.455G〉T were found in both of the two patients. The former one led to the formation of a premature termination codon at amino acid position 266 （p. R266＂） and the later one caused the change in the first nucleotide of exon 6, leading to an elimination of acceptor-splicing site of this exon. The healthy mother of patient one was a heterozygous carrier of the mutation c.455G〉T. However, the two mutations were not found in normal controls. Conclusion The mutation c.796C〉T and c.455G〉T in the SERPINB＇I gene are responsible for NPPK in the two patients.