Application of array-comparative genomic hybridization in tetralogy of Fallot.
Application of array-comparative genomic hybridization in tetralogy of Fallot.
复制标题
芯片比较基因组杂交在法洛四联症中的应用
DOI：
10.1097/md.0000000000005552
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发表时间：
2016-12
期刊：
影响因子：
1.6
通讯作者：
Wang CZ
中科院分区：
文献类型：
--
作者：
Liu L;Wang HD;Cui CY;Wu D;Li T;Fan TB;Peng BT;Zhang LZ;Wang CZ
为探讨法洛四联症（TOF）的发病机制，为遗传咨询和产前基因诊断提供参考依据，采用G显带核型分析和芯片比较基因组杂交（aCGH）技术，对86例TOF患者的染色体核型和全基因组拷贝数变异（CNVs）进行了分析。然后用定量聚合酶链反应对候选CNVs进行验证。根据CNVs的不同性质，将其分为良性CNVs、可疑致病性CNVs和不确定性CNVs。数据分析基于公共数据库，如UCSC、DECIPHER、DGV、ISCA和OMIM。86例TOF患者核型均正常。用aCGH和定量聚合酶链反应检测11例患者的CNVs。患者编号0001、0010和0029在染色体22q11.21区域有2.52-Mb缺失;患者编号0008在12p12.3p12.2和14q23.2q23.3区域分别有595-和428-kb重复;患者编号0009在1q21.1q21.2区域有1.46-Mb重复;患者编号0016在1q42.13区域有513-kb重复;患者编号0024在16q11.2区域有292-kb重复; 0026号患者在16q24.1区域有270-kb重复; 0028号患者在7q31.1区域有222-kb缺失; 0033号患者在17 q12区域有1.73-Mb重复; 0061号患者在1p36.33p36.31区域有5.79-Mb缺失。aCGH能准确检测TOF患者的CNVs。这有利于TOF的遗传咨询和产前诊断，为探讨先天性心脏病的发病机制提供了新的线索和理论依据。
Abstract To explore the underlying pathogenesis and provide references for genetic counseling and prenatal gene diagnosis, we analyzed the chromosome karyotypes and genome-wide copy number variations (CNVs) in 86 patients with tetralogy of Fallot (TOF) by G-banding karyotype analysis and array-comparative genomic hybridization (aCGH), respectively. And then quantitative polymerase chain reaction was used to validate these candidate CNVs. Based on their different properties, CNVs were categorized into benign CNVs, suspiciously pathogenic CNVs, and indefinite CNVs. Data analysis was based on public databases such as UCSC, DECIPHER, DGV, ISCA, and OMIM. The karyotype was normal in all the 86 patients with TOF. CNVs were detected in 11 patients by aCGH and quantitative polymerase chain reaction. Patient no. 0001, 0010, and 0029 had 2.52-Mb deletion in the chromosome 22q11.21 region; patient no. 0008 had both 595- and 428-kb duplications, respectively, in 12p12.3p12.2 and 14q23.2q23.3 regions; patient no. 0009 had 1.46-Mb duplication in the 1q21.1q21.2 region; patient no. 0016 had 513-kb duplication in the 1q42.13 region; patient no. 0024 had 292-kb duplication in the 16q11.2 region; patient no. 0026 had 270-kb duplication in the 16q24.1 region; patient no. 0028 had 222-kb deletion in the 7q31.1 region; patient no. 0033 had 1.73-Mb duplication in the 17q12 region; and patient no. 0061 had 5.79-Mb deletion in the 1p36.33p36.31 region. aCGH can accurately detect CNVs in the patients with TOF. This is conducive to genetic counseling and prenatal diagnosis for TOF and provides a new clue and theoretical basis for exploring the pathogenesis of congenital heart disease.