弹性假黄色瘤一例ABCC6基因突变分析

Mutation analysis of the ABCC6 gene in a patient with pseudoxanthoma elasticum

目的：报告1例弹性假黄色瘤，并检测ABCC6基因突变情况。方法分析1例弹性假黄色瘤先证者的临床资料，并收集其父母、儿子及100例无亲缘关系的健康对照的外周血，提取基因组DNA，PCR扩增ABCC6基因编码区31个外显子，并进行DNA直接测序与ABCC6编码蛋白质功能预测。结果先证者父母及儿子表型均正常。基因突变分析显示，先证者存在ABCC6基因c.373G〉A（p.E125K）和c.3703C〉T （p.R1235W）的复合杂合突变，先证者母亲为c.3703C〉T（p.R1235W）杂合突变携带者，先证者父亲和儿子为c.373G〉A（p.E125K）杂合突变携带者，而100例无亲缘关系的健康对照均未检测到该两种突变。物种间序列比对分析发现，ABCC6编码蛋白质第125位谷氨酸和第1235位精氨酸为进化高度保守的序列，SIFT和Polyphen-2软件预测c.373G〉A（p.E125K）和c.3703C〉T（p.R1235W）突变为有害变异位点。结论 ABCC6基因c.373G〉A（p.E125K）和c.3703C〉T（p.R1235W）的复合杂合突变可能是该例弹性假黄色瘤患者发病的原因。

Objective To report a case of pseudoxanthoma elasticum, and to analyze mutations of the ABCC6 gene in the family with pseudoxanthoma elasticum. Methods Clinical data were obtained from a female patient with pseudoxanthoma elasticum and analyzed. Blood samples were collected from the proband, her parents and son, as well as 100 unrelated healthy human controls. Genomic DNA was extracted from these blood samples. PCR was performed to amplify 31 exons of the ABCC6 gene followed by direct DNA sequencing. The function of the protein encoded by the ABCC6 gene was predicted. Results The phenotypes of the patient′s parents and son were all normal. Mutation analysis of the ABCC6 gene revealed compound heterozygous mutations c.373G 〉 A（p.E125K）and c.3703C 〉 T （p.R1235W） in the proband, a heterozygous mutation c.3703C 〉 T （p.R1235W） in the proband′s mother, and a heterozygous mutation c.373G〉A（p.E125K）in the proband′s father and son. However, neither of the above mutations was found in the 100 unrelated healthy controls. Interspecific sequence alignment showed that glutamic acid at position 125 and arginine at position 1235 of the protein encoded by the ABCC6 gene were highly evolutionarily conserved. As SIFT and Polyphen-2 softwares showed, the mutations c.373G 〉 A （p.E125K） and c.3703C 〉 T （p.R1235W） were both predicted to be detrimental variations. Conclusion The compound heterozygous mutations c.373G 〉 A （p.E125K） and c.3703C 〉 T （p.R1235W） in the ABCC6 gene may be responsible for the occurrence of pseudoxanthoma elasticum in this patient.