CAJ | 학술논문

目的应用全基因组微阵列芯片平台,对6例具有Pierre Robin序列征(Pierre Robin sequence,PRS)表型的新生儿进行全基因组拷贝数变异(copy number variations,CNVs)检测,以发现与PRS相关的准确定位. 方法对2009年6月至2010年5月复旦大学附属儿科医院新生儿病房收治的符合PRS表现的6例患儿进行研究.采用Cytogenetic Whole Genome芯片筛查全基因组CNVs,对发现的所有CNVs进行分析,参照国际基因组拷贝数变异多态性数据库除外正常人群多态性CNVs.结合已知PRS的相关区段进行分析,并与已发表文献进行比较. 结果 (1)6例患儿均具小下颌畸形、腭裂及舌后坠3种表型.此外,2例有其他特殊面容表现,2例有先天性心脏病,1例有先天性喉软骨发育不良,1例存在脉络膜多发囊性占位.(2)6例PRS患儿经微阵列芯片检测,最终获得7个罕见、有潜在临床意义的CNVs,分别为位于lp36.23-p26.22、l4q11.l-q11.2和20p13的重复,以及4q23、1 q43-q44的缺失各1例和l4q32.31的缺失2例.(3)文献比对分析显示,1q43-q44、14q32.31区段可能与PRS表型有关,1q43-q44区段包含与神经系统发育相关的基因AK T3和不均-核蛋白U(heterogeneous nuclear ribonucleoprotein U,hnRNPU)；14q32区段编码核仁小分子RNA,可能为基因组印迹区. 结论本研究提供了应用全基因组微阵列平台分析罕见、有潜在致病可能的CNVs方法,提示1q43-q44和14q32.31可能为与PRS有关的染色体区段.
목적 응용전기인조미진렬심편평태,대6례구유Pierre Robin서렬정(Pierre Robin sequence,PRS)표형적신생인진행전기인조고패수변이(copy number variations,CNVs)검측,이발현여PRS상관적준학정위. 방법 대2009년6월지2010년5월복단대학부속인과의원신생인병방수치적부합PRS표현적6례환인진행연구.채용Cytogenetic Whole Genome심편사사전기인조CNVs,대발현적소유CNVs진행분석,삼조국제기인조고패수변이다태성수거고제외정상인군다태성CNVs.결합이지PRS적상관구단진행분석,병여이발표문헌진행비교. 결과 (1)6례환인균구소하합기형、악렬급설후추3충표형.차외,2례유기타특수면용표현,2례유선천성심장병,1례유선천성후연골발육불량,1례존재맥락막다발낭성점위.(2)6례PRS환인경미진렬심편검측,최종획득7개한견、유잠재림상의의적CNVs,분별위위우lp36.23-p26.22、l4q11.l-q11.2화20p13적중복,이급4q23、1 q43-q44적결실각1례화l4q32.31적결실2례.(3)문헌비대분석현시,1q43-q44、14q32.31구단가능여PRS표형유관,1q43-q44구단포함여신경계통발육상관적기인AK T3화불균-핵단백U(heterogeneous nuclear ribonucleoprotein U,hnRNPU)；14q32구단편마핵인소분자RNA,가능위기인조인적구. 결론 본연구제공료응용전기인조미진렬평태분석한견、유잠재치병가능적CNVs방법,제시1q43-q44화14q32.31가능위여PRS유관적염색체구단.
Objective To screen for genomic copy number variants(CNVs)in six neonates with Pierre Robin sequence(PRS)by Affymetrix 2.7 M chip to identify possible loci related to PRS.Methods Six neonates with PRS admitted into the Department of Neonatology,Children's Hospital of Fudan University from June 2009 to May 2010 were enrolled in this study.CNVs were detected by Cytogenetic Whole Genome 2.7 M array.Rare CNVs with potential clinical significance that deletion segments' size ＞50 kb and duplication segments' size ＞200 kb were selected based on the analysis of Chromosome Analysis Suite(ChAS)software,false positive CNVs and segments of normal population were excluded.The identified CNVs were compared with those in relative published literatures.Results(1)Among 6 PRS patients,two patients had facial deformation,two had congenital heart defects,one had congenital dysplasia of the laryngeal cartilage and one had choroidal space occupying lesion.(2)Seven rare CNVs whose size from 51-11 956 kb were identified in four neonates,including a 739 kb duplication on lp26.23-p36.22,a 6273 kb deletion on lq43-44,a 51 kb and a 55 kb deletions on 14q32.31,a 1022 kb duplication on 14q11.1-11.2,a 11 956 kb duplication on 20p13 and a 105 kb deletion on 4q23.3.(3)Published literatures showed that deletions of 1q43-44 and 14q32.31 might relate to micro/retrognathia and abnormal palate.Region of chromosome 1q43-q44 contained AKT3 and heterogeneous nuclear ribonucleoprotein U(hnRNPU)genes,and the haploinsufficiency of AKT3 and hnRNPU genes might cause developmental human microcephaly and agenesis of the corpus callosum,speech delay and seizures respectively.Region of chromosome 14q32.31 contained some C/D small nucleolar RNA,and the human imprinted 14q32 domain shared common genomic features with the imprinted 15q11-q13 loci.Conclusions This study established a method to discover whole genome CNVs in identifying novel submicroscopic deletions and duplications.Reviewing of published literatures suggested that deletions of chromosome 1q43-q44 and 14q32.31 might cause Pierre Robin sequence.