Molck Miriam Coelho, Simioni Milena, Paiva Vieira Társis, Sgardioli Ilária Cristina, Paoli Monteiro Fabíola, Souza Josiane, Fett-Conte Agnes Cristina, Félix Têmis Maria, Lopes Monlléo Isabella, Gil-da-Silva-Lopes Vera Lúcia
Universidade Estadual de Campinas (UNICAMP), Departamento de Genética Médica, Campinas, SP, Brazil.
Centro de Atendimento Integral ao Fissurado Lábio Palatal (CAIF), Curitiba, PR, Brazil.
J Pediatr (Rio J). 2017 Sep-Oct;93(5):497-507. doi: 10.1016/j.jped.2016.11.007. Epub 2017 Mar 21.
To identify pathogenic genomic imbalances in patients presenting congenital heart disease (CHD) with extra cardiac anomalies and exclusion of 22q11.2 deletion syndrome (22q11.2 DS).
78 patients negative for the 22q11.2 deletion, previously screened by fluorescence in situ hybridization (FISH) and/or multiplex ligation probe amplification (MLPA) were tested by chromosomal microarray analysis (CMA).
Clinically significant copy number variations (CNVs ≥300kb) were identified in 10% (8/78) of cases. In addition, potentially relevant CNVs were detected in two cases (993kb duplication in 15q21.1 and 706kb duplication in 2p22.3). Genes inside the CNV regions found in this study, such as IRX4, BMPR1A, SORBS2, ID2, ROCK2, E2F6, GATA4, SOX7, SEMAD6D, FBN1, and LTPB1 are known to participate in cardiac development and could be candidate genes for CHD.
These data showed that patients presenting CHD with extra cardiac anomalies and exclusion of 22q11.2 DS should be investigated by CMA. The present study emphasizes the possible role of CNVs in CHD.
确定患有先天性心脏病（CHD）并伴有心脏外异常且排除22q11.2缺失综合征（22q11.2 DS）患者的致病基因组失衡情况。
对78例先前通过荧光原位杂交（FISH）和/或多重连接探针扩增（MLPA）筛查22q11.2缺失呈阴性的患者进行染色体微阵列分析（CMA）检测。
在10%（8/78）的病例中发现了具有临床意义的拷贝数变异（CNV≥300kb）。此外，在两例病例中检测到潜在相关的CNV（15q21.1区域993kb重复和2p22.3区域706kb重复）。本研究中在CNV区域内发现的基因，如IRX4、BMPR1A、SORBS2、ID2、ROCK2、E2F6、GATA4、SOX7、SEMAD6D、FBN1和LTPB1，已知参与心脏发育，可能是CHD的候选基因。
这些数据表明，对于患有CHD并伴有心脏外异常且排除22q11.2 DS的患者，应通过CMA进行研究。本研究强调了CNV在CHD中的可能作用。
