KMT2D基因突变所致的Kabuki综合征6例报告并文献复习
发布时间：2018-09-13 17:00
【摘要】：目的探讨KMT2D突变引起的Kabuki综合征(KS)的临床、遗传学特点及其在新生儿期的临床特征。方法采用全外显子组测序(WES)和临床panel的二代测序技术,结合复旦大学附属儿科医院分子诊断中心建立的数据分析流程,行相关基因测序和数据分析,对6例KMT2D基因突变患儿的临床及分子生物学特征进行总结。计算机检索Pub Med、中国知网、维普、中国生物医学文献和万方数据库,收集KS相关文献,检索时间从2012年4月至2017年4月,对描述新生儿期临床特征的文献进行提取、归纳和总结。结果 6例KS患儿,男4例,女2例。其中3例在婴儿期均因KS相关临床表现,家属要求行家系WES确诊,1例新生儿经临床panel检测后确诊,2例因家属要求对患儿进行WES测序确诊。6例KS患儿共检测到7个KMT2D基因的杂合突变,分别位于11、39、51和53号外显子,包括1个终止、4个错义和2个移码突变。其中c.12697CT(p.Q4233X)、c.16498CT(p.R5500W)、c.16273GA(p.E5425K)为人类基因突变数据库(HGMD)已收录的致病突变位点。c.12696GT(p.Q4232H)、c.3495del C(p.Pro1165Leufs Ter47)、c.10881del T(p.Leu3627Argfs Ter31)、c.12560GA(p.G418E)为新发突变位点。经SIFT、Polyphen 2和Mutation Taster软件预测为有害突变。纳入18篇KS新生儿期起病文献加上本文2例(34例),新生儿期表现为喂养困难(19例),心脏发育异常(20例),特殊容貌(17例),骨骼发育异常(15例),低血糖(10例)和肌张力低下(9例)等。结论 KS的典型临床表型在新生儿期还未完全呈现,当新生儿有喂养困难、心脏发育异常、特殊容貌等临床特征时需考虑KS,并尽早完善相关基因检测,实现早诊断、早干预。
[Abstract]:Objective to investigate the clinical and genetic characteristics of Kabuki syndrome (KS) caused by KMT2D mutation and its clinical features in neonatal stage. Methods the second generation sequencing technique of (WES) and clinical panel was used in the whole exon group, combined with the data analysis procedure established by the Molecular diagnosis Center of Pediatrics Hospital affiliated to Fudan University, and the related gene sequencing and data analysis were performed. The clinical and molecular biological characteristics of 6 children with KMT2D gene mutation were summarized. Pub Med, China knowledge Network, Weip, Chinese Biomedical Literature and Wanfang Database were searched by computer, and the related documents of KS were collected. The retrieval time was from April 2012 to April 2017, and the literature describing the clinical characteristics of newborn was extracted. Induction and summary. Results there were 6 cases of KS, including 4 males and 2 females. Among them, 3 cases were due to KS related clinical manifestations in infancy. The family requested that one newborn be diagnosed by clinical panel test in the family line WES. Two cases were diagnosed by WES sequencing. A total of 7 heterozygous mutations of KMT2D gene were detected in 6 cases of KS patients, which were located at exon 113951 and exon 53, respectively. Including 1 termination, 4 missense and 2 frameshift mutations. Among them, c.12697CT (p.Q4233X) / c. 16498CT (p.R5500W) / c. 16273GA (p.E5425K) is a new mutation locus, which is identified by (HGMD) as the pathogenicity mutation locus. C. 12696GT (p.Q4232H) / c. 3495del C (p.Pro1165Leufs Ter47) / c. 10881del T (p.Leu3627Argfs Ter31) / c. 12560GA (p.G418E). It was predicted by SIFT,Polyphen 2 and Mutation Taster software as harmful mutation. 18 articles on the onset of neonatal KS and 2 cases (34 cases) were included in this paper. The neonatal manifestations included feeding difficulties (19 cases), cardiac dysplasia (20 cases), special appearance (17 cases), skeletal dysplasia (15 cases), hypoglycemia (10 cases) and muscle tenderness. Low strength (9 cases). Conclusion the typical clinical phenotype of KS is not completely present in the neonatal stage. When the neonates have the clinical characteristics such as feeding difficulty, abnormal heart development and special appearance, we should consider KS, and improve the detection of relevant genes as soon as possible, so as to realize early diagnosis and early intervention.
【作者单位】： 复旦大学附属儿科医院上海市出生缺陷防治重点实验室 复旦大学儿童发育与疾病转化医学研究中心;卫生部新生儿疾病重点实验室;新疆维吾尔自治区人民医院新生儿科;
【基金】：上海市卫生和计划生育委员会基金面上项目:201440628
【分类号】：R722.1
[Abstract]:Objective to investigate the clinical and genetic characteristics of Kabuki syndrome (KS) caused by KMT2D mutation and its clinical features in neonatal stage. Methods the second generation sequencing technique of (WES) and clinical panel was used in the whole exon group, combined with the data analysis procedure established by the Molecular diagnosis Center of Pediatrics Hospital affiliated to Fudan University, and the related gene sequencing and data analysis were performed. The clinical and molecular biological characteristics of 6 children with KMT2D gene mutation were summarized. Pub Med, China knowledge Network, Weip, Chinese Biomedical Literature and Wanfang Database were searched by computer, and the related documents of KS were collected. The retrieval time was from April 2012 to April 2017, and the literature describing the clinical characteristics of newborn was extracted. Induction and summary. Results there were 6 cases of KS, including 4 males and 2 females. Among them, 3 cases were due to KS related clinical manifestations in infancy. The family requested that one newborn be diagnosed by clinical panel test in the family line WES. Two cases were diagnosed by WES sequencing. A total of 7 heterozygous mutations of KMT2D gene were detected in 6 cases of KS patients, which were located at exon 113951 and exon 53, respectively. Including 1 termination, 4 missense and 2 frameshift mutations. Among them, c.12697CT (p.Q4233X) / c. 16498CT (p.R5500W) / c. 16273GA (p.E5425K) is a new mutation locus, which is identified by (HGMD) as the pathogenicity mutation locus. C. 12696GT (p.Q4232H) / c. 3495del C (p.Pro1165Leufs Ter47) / c. 10881del T (p.Leu3627Argfs Ter31) / c. 12560GA (p.G418E). It was predicted by SIFT,Polyphen 2 and Mutation Taster software as harmful mutation. 18 articles on the onset of neonatal KS and 2 cases (34 cases) were included in this paper. The neonatal manifestations included feeding difficulties (19 cases), cardiac dysplasia (20 cases), special appearance (17 cases), skeletal dysplasia (15 cases), hypoglycemia (10 cases) and muscle tenderness. Low strength (9 cases). Conclusion the typical clinical phenotype of KS is not completely present in the neonatal stage. When the neonates have the clinical characteristics such as feeding difficulty, abnormal heart development and special appearance, we should consider KS, and improve the detection of relevant genes as soon as possible, so as to realize early diagnosis and early intervention.
【作者单位】： 复旦大学附属儿科医院上海市出生缺陷防治重点实验室 复旦大学儿童发育与疾病转化医学研究中心;卫生部新生儿疾病重点实验室;新疆维吾尔自治区人民医院新生儿科;
【基金】：上海市卫生和计划生育委员会基金面上项目:201440628
【分类号】：R722.1
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