KMT2D基因突變所致的Kabuki綜合征6例報告并文獻復(fù)習(xí)
發(fā)布時間：2018-09-13 17:00
【摘要】：目的探討KMT2D突變引起的Kabuki綜合征(KS)的臨床、遺傳學(xué)特點及其在新生兒期的臨床特征。方法采用全外顯子組測序(WES)和臨床panel的二代測序技術(shù),結(jié)合復(fù)旦大學(xué)附屬兒科醫(yī)院分子診斷中心建立的數(shù)據(jù)分析流程,行相關(guān)基因測序和數(shù)據(jù)分析,對6例KMT2D基因突變患兒的臨床及分子生物學(xué)特征進行總結(jié)。計算機檢索Pub Med、中國知網(wǎng)、維普、中國生物醫(yī)學(xué)文獻和萬方數(shù)據(jù)庫,收集KS相關(guān)文獻,檢索時間從2012年4月至2017年4月,對描述新生兒期臨床特征的文獻進行提取、歸納和總結(jié)。結(jié)果 6例KS患兒,男4例,女2例。其中3例在嬰兒期均因KS相關(guān)臨床表現(xiàn),家屬要求行家系WES確診,1例新生兒經(jīng)臨床panel檢測后確診,2例因家屬要求對患兒進行WES測序確診。6例KS患兒共檢測到7個KMT2D基因的雜合突變,分別位于11、39、51和53號外顯子,包括1個終止、4個錯義和2個移碼突變。其中c.12697CT(p.Q4233X)、c.16498CT(p.R5500W)、c.16273GA(p.E5425K)為人類基因突變數(shù)據(jù)庫(HGMD)已收錄的致病突變位點。c.12696GT(p.Q4232H)、c.3495del C(p.Pro1165Leufs Ter47)、c.10881del T(p.Leu3627Argfs Ter31)、c.12560GA(p.G418E)為新發(fā)突變位點。經(jīng)SIFT、Polyphen 2和Mutation Taster軟件預(yù)測為有害突變。納入18篇KS新生兒期起病文獻加上本文2例(34例),新生兒期表現(xiàn)為喂養(yǎng)困難(19例),心臟發(fā)育異常(20例),特殊容貌(17例),骨骼發(fā)育異常(15例),低血糖(10例)和肌張力低下(9例)等。結(jié)論 KS的典型臨床表型在新生兒期還未完全呈現(xiàn),當(dāng)新生兒有喂養(yǎng)困難、心臟發(fā)育異常、特殊容貌等臨床特征時需考慮KS,并盡早完善相關(guān)基因檢測,實現(xiàn)早診斷、早干預(yù)。
[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.
【作者單位】： 復(fù)旦大學(xué)附屬兒科醫(yī)院上海市出生缺陷防治重點實驗室 復(fù)旦大學(xué)兒童發(fā)育與疾病轉(zhuǎn)化醫(yī)學(xué)研究中心;衛(wèi)生部新生兒疾病重點實驗室;新疆維吾爾自治區(qū)人民醫(yī)院新生兒科;
【基金】：上海市衛(wèi)生和計劃生育委員會基金面上項目:201440628
【分類號】：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.
【作者單位】： 復(fù)旦大學(xué)附屬兒科醫(yī)院上海市出生缺陷防治重點實驗室 復(fù)旦大學(xué)兒童發(fā)育與疾病轉(zhuǎn)化醫(yī)學(xué)研究中心;衛(wèi)生部新生兒疾病重點實驗室;新疆維吾爾自治區(qū)人民醫(yī)院新生兒科;
【基金】：上海市衛(wèi)生和計劃生育委員會基金面上項目:201440628
【分類號】：R722.1
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