本文選題：胎兒水腫 + 致死性　； 參考：《中國循證兒科雜志》2017年04期

【摘要】：目的針對不明原因致死性胎兒水腫的患兒行全外顯子組測序,分析與胎兒水腫表型相關(guān)的潛在候選基因。方法收集2011年1月1日至2017年6月1日復(fù)旦大學(xué)附屬兒科醫(yī)院(我院)收治的不明原因致死性胎兒水腫并行全外顯子組檢測的病例,采集與致死性胎兒水腫有關(guān)的母親、圍生期和新生兒因素,按照我院轉(zhuǎn)化醫(yī)學(xué)中心建立的高通量測序數(shù)據(jù)分析流程,采用Ex AC數(shù)據(jù)庫、千人基因組數(shù)據(jù)庫和我院分子診斷中心已經(jīng)進(jìn)行建立的13 810例全外顯子組數(shù)據(jù),行后續(xù)數(shù)據(jù)分析。結(jié)果符合本文納入標(biāo)準(zhǔn)的不明原因致死性胎兒水腫患兒18例進(jìn)入本文分析,男、女各9例,胎齡(34±2)周,體重(2 935±911)g。2例患兒母親有因胎兒水腫或胸腔積液引產(chǎn)的不良孕產(chǎn)史,3例患兒為試管嬰兒。常見的臨床表型除胎兒水腫和羊水過多外,還包括心功能不全、休克和肺發(fā)育不全等。7例患兒檢測到符合罕見潛在致病標(biāo)準(zhǔn)的變異共9個。5例患兒檢測到的雜合變異,2個為有害變異(無義變異位于FOXF1基因,移碼變異位于RASA1基因),3個錯義變異(位于FOXC2基因)。2例患兒檢測到的雜合變異,4個變異位于PIEZO1基因2個均為有害變異,位于DSP基因的2個變異均為錯義變異。上述基因進(jìn)行通路富集分析發(fā)現(xiàn),多集中在心血管、血管和血管內(nèi)皮生長因子等通路上。結(jié)論在病因不明的致死性胎兒水腫病例中檢測到罕見潛在致病變異,結(jié)合既往報道文獻(xiàn),FLT4、SPTB、PIEZO1和FOXC2基因可考慮作為胎兒水腫候選基因;首次提出FOXF1、RASA1和DSP基因可能與胎兒水腫表型相關(guān)。
[Abstract]:Objective to analyze the potential candidate genes associated with fetal edema phenotype in children with unexplained fatal fetal edema.Methods from January 1, 2011 to June 1, 2017, the patients with unexplained fatal fetal edema and total exon group were collected from pediatric hospital affiliated to Fudan University (our hospital), and mothers associated with fatal fetal edema were collected.Perinatal and neonatal factors, according to the high-throughput sequencing data analysis process established by the Center for Transforming Medicine in our hospital, Ex AC database was used.The data of 13 810 cases of total exon set from the human genome database and the molecular diagnosis center of our hospital were analyzed.Results 18 children with unexplained fatal fetal edema, 9 male and 9 female, were included in the analysis. The gestational age was 34 鹵2 weeks.A total of 2 935 鹵911)g.2 cases of fetal edema or pleural effusion were found to have a history of poor pregnancy and labor. 3 cases were in vitro.In addition to fetal edema and amniotic fluid, common clinical phenotypes include cardiac dysfunction,Heterozygosity was detected in 9 out of 7 children with shock and pulmonary dysplasia, and 2 were deleterious (nonsense mutation located in FOXF1 gene).Frameshift mutation was located in RASA1 gene, and 3 missense mutations (located in heterozygosity of FOXC2 gene were detected in 2 cases of children with FOXC2 gene). The 4 mutations located in PIEZO1 gene were both deleterious and the 2 mutations in DSP gene were missense mutations.The results of pathway enrichment analysis showed that these genes were mainly concentrated in cardiovascular, vascular and vascular endothelial growth factor pathways.Conclusion A rare and potential mutation was detected in fatal fetal edema with unknown etiology. Combined with the previous literature, the gene of PIEZO1 and FOXC2 may be considered as candidate genes for fetal edema.It is suggested for the first time that FOXF1 RASA1 and DSP genes may be associated with fetal edema phenotype.
【作者單位】： 復(fù)旦大學(xué)附屬兒科醫(yī)院新生科;復(fù)旦大學(xué)附屬兒科醫(yī)院分子診斷中心;
【分類號】：R714.5
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本文編號：1761899