Chanarin-Dorfman综合征一例国内首报  

Chanarin-Dorfman syndrome:the first case reported in China

作　　者：刘依和 陈志明 杨勇 Liu Yihe;Chen Zhiming;Yang Yong(Genetic Skin Disease Center,Hospital of Dermatology,Chinese Academy of Medical Sciences and Peking Union Medical College,Nanjing 210042,China)

机构地区：[1]中国医学科学院、北京协和医学院皮肤病医院遗传病中心,南京210042

出　　处：《中华皮肤科杂志》2021年第8期673-676,共4页Chinese Journal of Dermatology

基　　金：国家自然科学基金 (81903195)。

摘　　要：目的检测1例以鱼鳞病伴肝功能异常为主要临床表现的家系基因突变情况,并明确其诊断。方法收集先证者临床资料,采集先证者及其父母外周血,提取基因组DNA,对先证者进行遗传性皮肤病目标基因外显子测序,确定突变位点,在家系中对突变位点进行Sanger测序验证,并对先证者及其父母外周血涂片等辅助检查结果进行分析。结果先证者全身皮肤干燥,下肢可见白色细小鳞屑,伴有转氨酶升高、双耳轻度感音神经性耳聋和脂肪肝。先证者外周血基因组DNA中编码CGI-58蛋白的ABHD5基因第6外显子存在纯合突变(c.933dupA),导致氨基酸序列发生移码突变(p.R312Tfs*45),其父亲、母亲该位点均为杂合突变,突变与疾病符合共分离。先证者外周血涂片发现中性粒细胞内含脂质空泡,即Jordan小体阳性。结论先证者表现为鱼鳞病样皮损和肝功能异常,结合其ABHD5基因纯合突变和外周血涂片Jordan小体阳性,诊断为Chanarin-Dorfman综合征。Objective To detect gene mutations and make a diagnosis in a family with ichthyosis accompanied by liver injury.Methods Clinical data were collected from the proband,and genomic DNA was extracted from peripheral blood samples from the proband and his parents.Exome sequencing was performed in the proband by using a gene panel targeting hereditary skin diseases to identify mutation sites,and then the candidate mutation site was verified by PCR and Sanger sequencing in the family members.Results of peripheral blood smear examination and other auxiliary examinations were collected from the proband and his parents and analyzed.Results The proband presented with generalized dry skin and tiny white scales on the lower limbs,accompanied by elevated transaminase levels,mild sensorineural hearing loss in both ears and fatty liver.Exome sequencing revealed a homozygous mutation c.933dupA in exon 6 of the ABHD5 gene encoding CGI-58 protein in the peripheral blood genomic DNA of the proband,resulting in a frameshift mutation p.R312Tfs*45 in the amino acid sequence.Heterozygous mutations at this site were identified in his father and mother.The mutation cosegregated with the disease phenotype in the family.The peripheral blood smear examination of the proband showed lipid vacuoles in neutrophils,which were called Jordan anomaly.Conclusion The diagnosis of Chanarin-Dorfman syndrome was made in the proband based on the presentation of ichthyosis-like skin lesions and abnormal liver function,as well as the homozygous mutation in the ABHD5 gene and Jordan anomaly in peripheral blood smears.

关 键 词：鳞癣样红皮病 先天性 肝功能不全 听觉丧失 感音神经性 DNA突变分析 Chanarin-Dorfman综合征 基因 ABHD5 Jordan小体 

分 类 号：R758.52[医药卫生—皮肤病学与性病学] R589.2[医药卫生—临床医学]