miRNA-548m调控SUMO1基因表达在胎儿唇腭裂的病因学研究  

Up-regulated SUMO1 expression by inhibition of miRNA-548m as a potential cause of congenital orofacial cleft in a fetus

作　　者：牛文彬[1] 霍明珠 徐家伟[1] 王芳[1] 赵艳萍[2] 史昊 刘益栋 孙莹璞[1] Niu Wenbin;Huo Mingzhu;Xu Jiawei;Wang Fang;Zhao Yanping;Shi Hao;Liu Yidong;Sun Yingpu(Center for Reproductive Medicine,Henan Key Laboratory of Reproduction and Genetics,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Department of Ultrasonography,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生殖医学中心,河南省生殖与遗传重点实验室,郑州450052 [2]郑州大学第一附属医院超声影像科,450052

出　　处：《中华医学遗传学杂志》2021年第7期647-651,共5页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划(2019YFA0110900);国家自然科学基金(81701443);中华医学会临床医学科研专项资金生殖医学青年医师研究与发展项目(17020250694)。

摘　　要：目的对1例超声显示唇腭裂胎儿进行遗传学检测,分析胎儿唇腭裂的遗传学病因。方法应用单核苷酸多态性微阵列技术(single nucleotide polymorphism array,SNP array)对引产胎儿皮肤标本进行基因组拷贝数变异检测,并分析变异区域基因致病性。结果SNP array检测显示唇腭裂胎儿基因组Xq21.31-q22.1(91063807-100293555)区域存在约9.23 Mb半合子缺失,其表型正常母亲该区域杂合缺失,该变异区域包括13个OMIM基因和1个非编码RNA(non-coding RNA,ncRNA)基因MIR548M,在人口腔上皮细胞系中抑制MIR548M编码的miRNA-548m后,唇腭裂相关基因SUMO1表达上调。结论抑制miRNA-548m导致唇腭裂相关基因SUMO1表达异常,SNP array检测发现的MIR548M基因缺失可能是导致胎儿发生唇腭裂的关键遗传学病因。Objective To explore the genetic etiology for a fetus with congenital orofacial cleft.Methods Single nucleotide polymorphism microarray(SNP array)was carried out on skin tissues sampled from the fetus following induced abortion for the detection of copy number variation(CNVs).Pathogenicity of the candidate gene was validated through experiment.Results SNP array revealed that the fetus has carried a hemizygous 9.23Mb deletion at Xq21.31-q22.1(91063807-100293555),which was inherited from its mother.The region contained 13 OMIM genes and 1 ncRNA-coding gene(MIR548M).Inhibiting of the expression of the MIR548M gene in oral epithelial celllines has resulted in up-regulation of the expression of SUMO1 gene which was known to involve in the pathogenesis of orofacial cleft.Conclusion Dosage insufficiency of the MIR548M gene may underlie the etiology of orofacial cleft in this fetus.

关 键 词：唇腭裂 单核苷酸多态性微阵列 基因组拷贝数变异 miRNA-548m SUMO1基因 

分 类 号：R714.5[医药卫生—妇产科学]