Genetic Analysis Strategy for Diagnosing Congenital Heart Disease

Congenital heart defects (CHD) affect approximately 10-12 per 1,000 newborns globally, and they can be divided into simple cardiac defects or severe and complex ones. Its etiology derives from environmental and genetic causes, with 20-30% of cases being genetic conditions ranging from alterations such as aneuploidies, monogenic defects, and copy number variations (CNVs). Even with the severity of this condition, many patients remain with an uncertain diagnosis. This study aimed to evaluate patients with CHD who are still undiagnosed but have already undergone genetic testing and evaluation and provide a guideline that can be followed in third-world countries to make CHD diagnostics faster and easier.

DNA was extracted from all patients included; first the samples were analyzed with the P311 multiplex ligation-dependent probe amplification (MLPA) kit specific to CHD, and the patients that remain undiagnostic were analyzed with the P245 MLPA kit for microdeletions.

CNVs were identified in 36% of the patients, representing a high detection rate.

The patient selection and prior clinical evaluation may explain our high detection rate, as much as the karyotype and fluorescent in situ hybridization normal results used for screening, combined with using two MLPA kits for detection.