肠病性肢端皮炎SLC39A4基因突变的研究

A study of SLC39A4 gene mutation responsible for acrodermatitis enteropathica

目的:研究肠病性肢端皮炎(acrodermatitis enteropathica,AE)患者SLC39A4基因突变情况,为完善该病的基因诊断与遗传咨询提供分子生物学依据。方法:提取AE家系成员(包括1例男性AE患者及其双亲)和100例正常对照外周血白细胞基因组DNA,PCR扩增SLC39A4基因的全部外显子并行DNA测序。结果:检测到患者SLC39A4基因中第5号外显子c.831G>A和第10号外显子c.1617delA,前者导致编码蛋白密码子277位ATG变为ATA,编码的蛋氨酸Methionine M变为异亮氨酸Isoleucine I,后者导致cDNA1617位A丢失,移码突变。患者的父亲和母亲分别携带c.831G>A和c.1617delA基因突变,与家系无血缘关系的100名正常对照均未发现此突变。结论:SLC39A4基因c.831G>A和c.1617delA突变是导致该例患者AE的特异突变。

Objective：To analyze the SLC39A4 gene mutation and mutating patterns in a sporadic Chinese patient with acrodermatitis enteropathica （AE） so as to provide a basis for gene diagnosis and genetic counseling of the disorder. Methods：Genomic DNA was extracted from whole blood by standard methods from one male AE patient and his parents. DNA samples were also extracted from 100 unrelated,normally individuals as controls. The whole coding region of SLC39A4 was amplified by PCR and products were analyzed by direct sequencing. Results：Molecular analysis of the SLC39A4 gene in this case of AE revealed a novel heterozygous mutation c.831G〉A in exon 5 and c.1617delA in exon 10,which altered a methionine residue with isoleucine residue at position 277 of the protein sequence and caused a reading frame shift,respectively. The patient’s father was found to only carry heterozygous c.831G〉A mutation,while his mother carried heterozygous c.1617delA mutation. The two novel mutations were not observed in 100 control individuals selected from a Chinese population. Conclusion：Our data suggest that c.831G〉A and c.1617delA mutation of SLC39A4 gene is the genetic cause of AE.