Rare De Novo Copy Number Variants in Patients with Congenital Pulmonary AtresiaReportar como inadecuado

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Ongoing studies using genomic microarrays and next-generation sequencing have demonstrated that the genetic contributions to cardiovascular diseases have been significantly ignored in the past. The aim of this study was to identify rare copy number variants in individuals with congenital pulmonary atresia PA.

Methods and Results

Based on the hypothesis that rare structural variants encompassing key genes play an important role in heart development in PA patients, we performed high-resolution genome-wide microarrays for copy number variations CNVs in 82 PA patient-parent trios and 189 controls with an Illumina SNP array platform. CNVs were identified in 17-82 patients 20.7%, and eight of these CNVs 9.8% are considered potentially pathogenic. Five de novo CNVs occurred at two known congenital heart disease CHD loci 16p13.1 and 22q11.2. Two de novo CNVs that may affect folate and vitamin B12 metabolism were identified for the first time. A de novo 1-Mb deletion at 17p13.2 may represent a rare genomic disorder that involves mild intellectual disability and associated facial features.


Rare CNVs contribute to the pathogenesis of PA 9.8%, suggesting that the causes of PA are heterogeneous and pleiotropic. Together with previous data from animal models, our results might help identify a link between CHD and folate-mediated one-carbon metabolism FOCM. With the accumulation of high-resolution SNP array data, these previously undescribed rare CNVs may help reveal critical genes in CHD and may provide novel insights about CHD pathogenesis.

Autor: Li Xie, Jin-Lan Chen, Wei-Zhi Zhang, Shou-Zheng Wang, Tian-Li Zhao, Can Huang, Jian Wang, Jin-Fu Yang, Yi-Feng Yang , Zhi-Ping Ta

Fuente: http://plos.srce.hr/


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