ADAR基因新发突变致遗传性对称性色素异常症一家系研究  

Dyschromatosis symmetrical hereditaria caused by mutation of ADAR gene in a pedigree

作　　者：王彩云 刘莉娜 黄茂欣 于建斌[1] WANG Cai-yun;LIU Li-na;HUANG Mao-xin;YU Jian-bin(Department of Dermatology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Institute of Genetics and Prenatal Diagnosis,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院皮肤科,河南郑州450052 [2]郑州大学第一附属医院遗传与产前诊断中心,河南郑州450052

出　　处：《中华实用诊断与治疗杂志》2021年第9期912-915,共4页Journal of Chinese Practical Diagnosis and Therapy

基　　金：河南省研究生创新培养基地建设项目(YJSCXJD201908)。

摘　　要：目的探讨一家系2例遗传性对称性色素异常症患者基因突变情况。方法收集一家系2例遗传性对称性色素异常症患者的临床资料。采集该家系先证者及其父母、100例健康对照者外周血,提取基因组DNA,采用高通量测序法检测皮肤病相关基因各外显子编码区域序列,应用PCR-Sanger测序验证突变基因,应用GERP++、PyMOL、SPIDEX、SIFT和Polyphen等生物信息软件预测突变基因编码的蛋白结构及致病性。结果先证者临床表现为双手背及足背对称性褐色色素沉着斑和色素减退斑,先证者父亲临床表现为面部、双侧锁骨、双手背及腕部、双足背及踝部对称性褐色色素沉着斑和色素减退斑,该家系3代以内其他成员均无类似皮损表现。基因测序结果显示,先证者及其父亲RNA特异性腺苷脱氨酶(adenosine deaminase acting on RNA,ADAR)基因第2外显子发生c.716G>A(p.Arg239Gln)杂合错义突变,导致其编码蛋白的第239位氨基酸由Arg突变为Gln;先证者母亲及100例健康对照者均未发现该突变。生物信息软件预测结果显示,ADAR基因突变后对应蛋白结构发生变化,该位点突变为疑似致病性突变。结合患者临床表现、基因测序及软件分析结果,诊断为遗传性对称性色素异常症。结论ADAR基因c.716G>A(p.Arg239Gln)杂合错义突变可能是该家系2例遗传性对称性色素异常症患者的致病原因。Objective To study the gene mutations of two patients with dyschromatosis symmetrical hereditaria in a pedigree.Methods The clinical data of two patients with dyschromatosis symmetrical hereditaria in a family were collected.The genomic DNAs of blood were extracted from the proband,his parents and 100 healthy controls.High-throughput sequencing was used to detect the sequence variation of dermatosis related genes in the proband’s family,while PCR-Sanger sequencing was used to verify the mutant gene.The softwares as GERP++,PyMOL,SPIDEX,SIFT and Polyphen were used to predict the protein function of mutant gene.Results The clinical manifestations were symmetrical brown hyperpigmentation and hypopigmentation on the dorsal aspects of both hands and feet of the proband,symmetrical brown hyperpigmented and hypopigmented macules on the face,bilateral clavicles,the dorsal aspects of both hands and wrists,the dorsal aspects of both feet and ankle joints of the proband’s father,which were not found in the members within 3 generations of this family.Gene testing indicated that the proband and his father carried a heterozygous missense mutation c.716 G>A(p.Arg239 Gln)in exon 2 of ADAR gene,resulting in the mutation of arginine to glutamine at position 239 of the encoded protein.No mutation was found in the proband’s mother and 100 healthy controls.Bioinformatics software analysis showed that the corresponding protein structure changed after gene mutation,which was suspected the pathogenicity mutation.The clinical manifestations combined with gene detection and software analysis confirmed the final diagnosis of dyschromatosis symmetrical hereditaria.Conclusion The c.716 gG>A(p.Arg239 Gln)mutation of ADAR gene may be the cause of the dyschromatosis symmetrical hereditaria of these two patients in this family.

关 键 词：遗传性对称性色素异常症 RNA特异性腺苷脱氨酶基因 杂合突变 

分 类 号：R758.5[医药卫生—皮肤病学与性病学]