ZMPSTE24基因突变致限制性皮病1例病例报告并文献复习

doi:10.3969/j.issn.1673-5501.2019.04.012

摘要/Abstract

摘要： 目的报告1例ZMPSTE24基因突变致胎儿死亡的限制性皮病(RD)病例,总结临床特征及基因突变的特点,为产前咨询提供依据。方法对1例ZMPSTE24基因突变的RD患儿的临床资料和测序结果进行分析,结合人类基因突变数据库(HGMD)和PubMed,对ZMPSTE24基因突变所致疾病临床表型进行文献复习。结果男,死胎,G1P1。母亲孕27周行超声检查,胎儿臀位、羊水过少、羊水指数1.9 cm、胎儿右侧胸腔少量积液。孕31⁺³周因胎膜早破入院,伴妊娠期糖尿病,超声示胎儿宫内重度生长受限。孕32⁺²周娩出一男死胎,具有典型RD表型。为明确病因诊断行新生儿panel测序并行Sanger测序验证,检测到ZMPSTE24基因的一个纯合移码突变(c.1085dupT,p.Leu362PhefsTer19),为已报道的RD热点突变,突变频率达57.14%。检索HGMD和PubMed,共检索到ZMPSTE24基因的32种致病突变(63例),导致4种不同的疾病表型。检索万方、中国知网和PubMed数据库,检索时间从建库至2019年7月25日,共有49例(包括本文1例)ZMPSTE24突变导致RD。ZMPSTE24突变的临床表型严重程度与锌金属蛋白酶活性和核纤层蛋白前体蛋白的堆积程度相关。结论本例检测到的Leu362PhefsTer19突变为ZMPSTE24基因热点突变,ZMPSTE24基因型与临床表型呈高度相关。本研究提示妊娠期胎儿发育异常应注意RD可能,基因检测可明确诊断。早期基因诊断可为临床及时干预和遗传咨询提供依据。

关键词: ZMPSTE24基因, 限制性皮病, 酶活性, 基因型, 表型

Abstract: Objective To summarize the clinical features and the characteristics of a mutation in ZMPSTE24 gene in a stillborn fetus with restrictive dermopathy (RD), and to provide evidence for prenatal counseling.Methods We analyzed the clinical and genetic data of the stillborn fetus with RD. According to HGMD and PubMed,literature on clinical symptoms of the diseases caused by ZMPSTE24 mutation was reviewed.Results The neonate panel sequencing combined Sanger sequencing in proband and parents confirmed a homozygous frameshift mutation in ZMPSTE24 gene (c.1085dupT,p.Leu362PhefsTer19), which has been reported as a disease-causing mutation of RD and the hotspot mutation with high frequency up to 57.14%. Searching from HGMD and PubMed with "ZMPSTE24", and 32 disease-causing mutations were found to be related to 4 types of diseases. Up to July 2019, a total of 63 cases that caused by ZMPSTE24 mutations were retrieved in PubMed while there is no domestic report in Wanfang and CNKI database. The 49 cases of RD were summarized in this article. The severity of diseases caused by the mutation in ZMPSTE24 gene has a high correlation with the activity of zinc metalloprotease and the accumulation of prelamin A.Conclusion Leu362PhefsTer19 detected in this stillborn neonate is a hotspot mutation in ZMPSTE24 gene. The genotype of ZMPSTE24 gene is closely related to the phenotype. This article suggests that abnormal fetal development may consider the possibility of RD. The genetic test provides the basis not only for accurate diagnosis of RD but also for the appropriate intervention and family genetic counseling.

Key words: ZMPSTE24 gene, Restrictive dermopathy, Enzymatic activity, Genotype, Phenotype

赵得雄, 王晴, 彭小敏, 海妤婷, 马力刚, 汪悦, 王生兰, 王慧君, 吴冰冰. ZMPSTE24基因突变致限制性皮病1例病例报告并文献复习[J]. 中国循证儿科杂志, 2019, 14(4): 303-307.

ZHAO De-xiong, WANG Qing, PENG Xiao-min, HAI Yu-ting, MA Li-gang, WANG Yue, WANG Sheng-lan, WANG Hui-jun, WU Bing-bing. Restrictive dermopathy caused by a mutation in ZMPSTE24 gene: a case report and genotype-phenotype correlation analysis[J]. Chinese Journal of Evidence-Based Pediatrics, 2019, 14(4): 303-307.

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