PPM1D基因突变致Jansen-de Vries综合征临床表型与基因型特点分析  

Analysis of clinical phenotype and genotype of Jansen-de Vries syndrome caused by PPM1D gene mutation

作　　者：梅道启 王媛[1] 陈国洪 梅世月 杨秀安 郝新征 李艳娜[5] 王潇娜 张耀东 Mei Daoqi;Wang Yuan;Chen Guohong;Mei Shiyue;Yang Xiuan;Hao Xinzheng;Li Yanna;Wang Xiaona;Zhang Yaodong(Department of Neurology,Children′s Hospital Affiliated to Zhengzhou University,Henan Children′s Hospital,Zhengzhou Children′s Hospital,Zhengzhou 450018,China;Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases,Henan Engineering Research Center of Childhood Neurodevelopment,Zhengzhou 450018,China;Department of Biochemistry,School of Basic Medical Science,Chengde Medical University,Chengde 067000,China;Department of Pediatrics,Pingdingshan Hospital of Traditional Chinese Medicine,Pingdingshan 467000,China;Department of Pediatrics,Jiaxian Maternal and Child Health Hospital,Pingdingshan 467100,China)

机构地区：[1]郑州大学附属儿童医院(河南省儿童医院,郑州儿童医院)东区神经内科,郑州450018 [2]河南省遗传代谢性疾病重点实验室,河南省儿童神经发育工程研究中心,郑州450018 [3]承德医学院基础医学院生物化学教研室,067000 [4]河南省平顶山市中医院儿科,467000 [5]河南省郏县妇幼保健院儿科,平顶山467100

出　　处：《中华神经科杂志》2021年第11期1140-1147,共8页Chinese Journal of Neurology

基　　金：国家自然科学基金(81701125,81901387);河南省医学科技攻关联合共建项目(LHGJ20200618,2018020633);河南省高等学校重点科研项目计划(18A310029);河南省儿童神经发育工程研究中心开放课题(SG201907)。

摘　　要：目的探讨1例Jansen-de Vries综合征患儿的临床表型,明确其基因诊断及遗传学特点,提高临床上对本病的认识。方法收集郑州大学附属儿童医院2019年10月确诊的1例Jansen-de Vries综合征患儿的临床资料,采用核心家系全外显子基因组检测(Trio-WES)及染色体拷贝数变异(CNV)分析技术,对患儿及其父母进行基因检测,采用一代Sanger测序法对发现可能存在的致病突变进行家系成员验证,并进行临床和分子遗传学分析。结合PPM1D基因突变智力障碍患者的相关报道进行文献复习。结果先证者女童,11个月,临床表现为智力障碍,语言及运动发育落后,自闭行为,胃肠功能障碍,身材矮小;鼻梁低平,低位耳,短指综合征。患儿核心家系Trio-WES结果提示:PPM1D基因新生移码杂合突变PPM1D(NM-003620):c.1216delA(p.Thr406Profs*3),染色体核型及染色体CNV分析正常。文献检索目前共报道有18例PPM1D基因突变的智力障碍患者,在在线人类孟德尔遗传数据库中描述为智力发育障碍伴胃肠道功能紊乱和痛觉阈值升高,其年龄分布在7个月至21岁,临床表现为智力障碍、疼痛阈值增高、行为异常、喂养困难、视力障碍、短指综合征、身材矮小、发热或呕吐及先天性发育畸形等相关的一组综合征。结论Jansen-de Vries综合征临床主要表现为全面性发育迟缓(智力障碍/运动发育迟缓、语言发育落后、肌张力低下),行为异常(孤独样行为、自闭症),颅面发育畸形(前额宽阔、鼻梁低平、低位耳、上唇薄),短指综合征(短脚、小手指粗短),胃肠功能紊乱(溢奶、喂养困难、便秘)。患儿诊断为PPM1D基因新发移码杂合突变变异,目前的治疗方式以康复训练为主,部分矮小症可予生长激素替代治疗,PPM1D基因[PPM1D(NM-003620):c.1216delA(p.Thr406Profs*3)]是该患儿的遗传学病因。Objective To investigate the clinical phenotype of a child with Jansen-de Vries syndrome,to clarify its genetic diagnosis and genetic characteristics,and to improve the understanding of this disease.Methods Clinical data from a child with Jansen-de Vries syndrome diagnosed in the Children′s Affiliated Hospital of Zhengzhou University in October 2019 were collected,using core family-complete exon genomics detection(Trio-WES)and chromosome copy number variation(CNV)analysis techniques for genetic testing for the child and her parents,generation Sanger sequencing for family member verification for possible pathogenic mutations,and clinical and molecular genetic analysis.The relevant reports of PPM1D gene mutation in patients with mental retardation were reviewed.Results The proband was a 11-month-old girl,presenting with mental retardation,lagging speech and motor development,autistic behavior,gastrointestinal dysfunction,and short stature,low flat nose bridge,low ear,short finger syndrome.Trio-WES results of the core family of the child suggested that PPM1D was a new transcoding heterozygous mutation,PPM1D(NM-003620):c.1216delA(p.Thr406Profs*3),and the karyotype and CNV analysis of the chromosome were normal.Literature retrieval showed currently a total of 18 cases were reported PPM1D gene mutation of mental disorders,described in the online human Mendel database for developmental disorder associated with gastrointestinal dysfunction and pain threshold increases,the age distribution in the seven months to 21 years of age,clinical manifestation of mental retardation,increased pain threshold,abnormal behavior,feeding difficulties,visual impairment,short finger syndrome,a group of syndromes associated with short stature,fever or vomiting,and congenital deformities.Conclusions Jansen-de Vries syndrome clinically presents mainly with overall retardation(mental retardation/backward delayed motor development,language development,low muscle tone),abnormal behavior(lonely sample behavior,autism),craniofacial malformations

关 键 词：Jansen-de Vries综合征 PPM1D基因 高疼痛阈值 智力低下 变异 

分 类 号：R725.9[医药卫生—儿科]