MVD基因突变所致不同临床表型的2个汗孔角化症家系  

Different Clinical Phenotypes of Two Chinese Families with Porokeratosis Caused by Mevalonate Diphosphate Decarboxylase( MVD) Gene Mutations

作　　者：朱培秋 闫慧敏[1] 赵慧娟 郭独一 姜薇[1] ZHU Peiqiu, YAN Huimin, ZHAO Huijuan, GUO Duyi, JIANG Wei(Department of Dermatology,Peking University Third Hospital,Beijing 100191,Chin)

机构地区：[1]北京大学第三医院皮肤科,北京100191

出　　处：《中国皮肤性病学杂志》2018年第8期868-872,共5页The Chinese Journal of Dermatovenereology

基　　金：国家自然科学基金(81201216)

摘　　要：目的鉴定2个汗孔角化症家系的致病基因,并分析基因型与临床表型的关系。方法收集2个汗孔角化症家系的临床资料,提取外周血DNA,针对疾病相关基因测序分析,发现可疑致病性突变位于MVD基因,采用PCR扩增先证者及家系中患者MVD基因13个外显子及其侧翼序列测序验证,并以100例健康人作为对照。结果 2个家系均符合常染色体显性遗传模式。发现家系1先证者MVD基因第1号外显子的第1位核苷酸A发生突变(c.1A>G),导致氨基酸序列发生错义突变(p.M1V),家系中其他7例患者均带有该突变位点。发现家系2先证者MVD基因第7号外显子的第746号核苷酸T发生突变(c.746T>C),导致氨基酸序列发生错义突变(p.P249S),家系中其他2例患者均带有该突变位点。2个家系突变位点与疾病符合共分离,家系中健康成员及100例健康对照者均未发现相应突变。结论 MVD基因的错义突变(p.M1V;p.P249S)是导致2个家系汗孔角化症发病的特异性突变。Objective To identify the pathogenic gene mutations in two Chinese families with porokeratosis and analyze their relationship with clinical manifestation. Methods Clinical data of the two families with porokeratosis were collected and genomic DNA was extracted from peripheral blood leukocyte. By sequencing and analyzing the related gene with porokeratosis,the suspicious pathogenic gene was MVD gene. All the 13 coding exons and their flanking sequences of the MVD gene were subjected to PCR for amplifying and DNA sequencing was followed. One hundred normal individuals were also sequenced to exclude single nucleotide polymorphism. Results All the affected members of the first family had a heterozygous A〉G substitution at position c.1 in exon 1 of the MVD gene while all the affected members of the second family had a heterozygous T〉C substitution at position c.746 in exon 7 of the MVD gene. These mutations were not detected in both normal members of the two families,nor in the 100 healthy controls. Conclusion The heterozygous mutation p.M1V and p.F249S in MVD may cause the clinical manifestation of porokeratosis in the two pedigrees.

关 键 词：汗孔角化症 MVD基因突变 临床表现 

分 类 号：R758.5[医药卫生—皮肤病学与性病学]