Open AccessExperience with genomic sequencing in pediatric patients with congenital cardiac defects in a large community hospital
Author(s) -
Hauser Natalie S.,
Solomon Benjamin D.,
Vilboux Thierry,
Khromykh Alina,
Baveja Rajiv,
Bodian Dale L.
Publication year - 2018
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.357
Subject(s) - proband , etiology , medicine , exome sequencing , genetic testing , bioinformatics , gene , genetics , phenotype , mutation , biology
Background Congenital cardiac defects, whether isolated or as part of a larger syndrome, are the most common type of human birth defect occurring on average in about 1% of live births depending on the malformation. As there is an expanding understanding of the underlying molecular mechanisms by which a cardiac defect may occur, there is a need to assess the current rates of diagnosis of cardiac defects by molecular sequencing in a clinical setting. Methods and Results In this report, we evaluated 34 neonatal and pediatric patients born with a cardiac defect and their parents using exomized preexisting whole genome sequencing ( WGS ) data to model clinically available exon‐based tests. Overall, we identified candidate variants in previously reported cardiac‐related genes in 35% (12/34) of the probands. These include clearly pathogenic variants in two of 34 patients (6%) and variants of uncertain significance in relevant genes in 10 patients (26%), of these latter 10, 2 segregated with clinically apparent findings in the family trios. Conclusions These findings suggest that with current knowledge of the proteins underlying CHD , genomic sequencing can identify the underlying genetic etiology in certain patients; however, this technology currently does not have a high enough yield to be of routine clinical use in the screening of pediatric congenital cardiac defects.