Aleksandra Miletic1, Jelena Ruml Stojanovic1, Vojislav Parezanovic2,3, Snezana Rsovac4, Danijela Drakulic5, Ivan Soldatovic6, Marija Mijovic1, Brankica Bosankic1, Hristina Petrovic1, Nikola Borlja7, Milena Milivojevic5, Ana Marjanovic2, Marija Brankovic2, Goran Cuturilo8,9. 1. Department of Clinical Genetics, University Children's Hospital, Belgrade, Serbia. 2. Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 3. Department of Cardiology, University Children's Hospital, Belgrade, Serbia. 4. Department of Pediatric and Neonatal Intensive Care, University Children's Hospital, Belgrade, Serbia. 5. Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia. 6. Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 7. Centogene, Rostock, Germany. 8. Department of Clinical Genetics, University Children's Hospital, Belgrade, Serbia. gcuturilo@gmail.com. 9. Faculty of Medicine, University of Belgrade, Belgrade, Serbia. gcuturilo@gmail.com.
Abstract
Rapid and efficient diagnostics is crucial for newborns with congenital heart defects (CHD) in intensive care unit (ICU) but is often challenging. Given that genetic factors play a role in 20-30% cases of CHD, it is likely that genetic tests could improve both its speed and efficiency. We aimed to analyze the utility of rapid and cost-effective multiplex ligation dependent probe amplification analysis (MLPA) for chromosomal analysis in newborns with critical CHD. One hundred consecutive newborns admitted with critical CHD to the ICU were included in the study. Those with normal MLPA findings were further tested by chromosomal microarray and clinical exome sequencing. Overall, pathogenic/likely pathogenic variants were determined in ten (10%) newborns by MLPA, three (3%) by chromosomal microarray, and three (3%) by clinical exome sequencing. The most common variant detected was deletion of 22q11.2 region. Conclusion: MLPA is fast and cost-effective analysis that could be used as the first-tier test in newborns with critical CHD admitted to the ICU. What is Known: • MLPA is an established method for chromosome analysis in patients with CHD, but detection rate in newborns with critical CHD is unknown. What is New: • Study suggests that detection rate of casual variants using MLPA in newborns with critical CHD is 10%.
Rapid and efficient diagnostics is crucial for newborns with congenital heart defects (CHD) in intensive care unit (ICU) but is often challenging. Given that genetic factors play a role in 20-30% cases of CHD, it is likely that genetic tests could improve both its speed and efficiency. We aimed to analyze the utility of rapid and cost-effective multiplex ligation dependent probe amplification analysis (MLPA) for chromosomal analysis in newborns with critical CHD. One hundred consecutive newborns admitted with critical CHD to the ICU were included in the study. Those with normal MLPA findings were further tested by chromosomal microarray and clinical exome sequencing. Overall, pathogenic/likely pathogenic variants were determined in ten (10%) newborns by MLPA, three (3%) by chromosomal microarray, and three (3%) by clinical exome sequencing. The most common variant detected was deletion of 22q11.2 region. Conclusion:MLPA is fast and cost-effective analysis that could be used as the first-tier test in newborns with critical CHD admitted to the ICU. What is Known: • MLPA is an established method for chromosome analysis in patients with CHD, but detection rate in newborns with critical CHD is unknown. What is New: • Study suggests that detection rate of casual variants using MLPA in newborns with critical CHD is 10%.
Entities:
Keywords:
Congenital heart defects; Intensive care unit; MLPA