2个遗传对称性色素异常症家系新发基因突变及临床特征分析  

Analysis of New Gene Mutations and Clinical Features in Two Pedigrees with Dyschromatosis Symmetrics Hereditarian

作　　者：张高磊[1] 顾菲[1] 苏伟[1] 杨明 朱芸 刘燕 秦琴 刘晓雁[1] Zhang Gaolei;Gu Fei;Su Wei;Yang Ming;Zhu Yun;Liu Yan;Qin Qin;Liu Xiaoyan(Capital Institute of Pediatrics,Beijing 100020,China)

机构地区：[1]首都儿科研究所,北京100020

出　　处：《中国中西医结合皮肤性病学杂志》2021年第4期362-366,共5页Chinese Journal of Dermatovenereology of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金(编号:81974473,82073461)。

摘　　要：目的回顾总结2个皮肤异色家系基因突变及临床特征。方法采用聚合酶链反应(PCR)扩增2个皮肤异色家系中患者和正常人ADAR、KITLG/ADAM10、ABCA6、POLA1、RECQL4和ANAPC1基因所有外显子。应用Sanger法测序皮肤异色相关基因序列,与Ensembl和NCBI dbSNP基因数据库比对确定筛选可疑致病位点,根据美国医学遗传学与基因组学学会(ACMG)指南判定基因变异的致病性。对2个家系所有成员进行专科检查及病史问诊总结,概括总结2个遗传对称性色素异常症(DSH)家系临床特征。结果2个皮肤异色家系中所有患者发现了ADAR基因突变,家系1为ADAR基因10号外显子发生基因缺失,c.2763-8_2768delTTTTGTAGGTTTCT,导致氨基酸剪接突变;家系2为ADAR基因6号外显子发生基因点突变,c.2096C>G导致氨基酸改变(p.S699X);2个家系患者均表现为肢端对称性黑褐色色素沉着斑和色素脱失斑,面部黄褐色色素沉着斑;其中家系1患者除了皮肤异色还有听力减退和频繁发烧。结论2个皮肤异色家系中所有患者临床诊断为DSH,听力减退和频繁发烧或许由ADAR基因的10号外显子缺失所致。Objective In order to retrospective summarize the gene mutation and clinical features of two pedigrees with poikiloderma.Methods All exons of ADAR,KITLG/ADAM10,ABCA6,POLA1,RECQL4 and ANAPC1 genes were amplified by polymerase chain reaction(PCR),and sequenced by Sanger,the database of Ensembl and NCBI dbSNP were compared to identify the suspected pathogenic gene mutations.The pathogenicity of gene mutations was determined according to American College of Medical Genetic and Genomics(ACMG)guidelines.The clinical features of two pedigrees were summarized.Results Mutation of ADAR gene was found in all the patients of two pedigrees.Pedigree 1 had gene mutation of exon 10 of ADAR gene,c.2763-8_2768delTTTTGTAGGTTTCT,resulting in splicing site mutant affecting amino acid residues;pedigree 2 had gene mutation in exon 6 of ADAR gene,c.2096 C>G,resulting in amino acid muation(p.s699x).All patients showed symmetrical dark brown pigmented and depigmented macules on the extremities,and yellowish brown pigmented macules on the face;except for poikiloderma,hearing loss and frequent fever were found in pedigree 1.Conclusion The diagnosis of dyschromatosis symmetries hereditarian(DSH)in two poikiloderma pedigrees was confirmed by gene sequencing.Hearing loss and frequent fever may be caused by gene deletion of ADAR exon 10.

关 键 词：遗传 色素异常 基因突变 临床特征 

分 类 号：R758.54[医药卫生—皮肤病学与性病学]