[Introduction]: Newborn screening is a publicly-funded health program for the diagnosis and intervention of genetic disorders that may otherwise have serious clinical consequences. In order to reduce false positives and negatives, shorten diagnosis time and provide genetic counseling, we are evaluating next generation sequencing (NGS) as a second-tier test. [Methods]: We use dried blood spot samples from positively-identified newborns to prepare NGS libraries. We have developed a panel of 71 genes commonly affected in the disorders detected by these programs. A bioinformatics pipeline identifies rare genetic variants that may be disease causing. Following technical validation, we have retrospectively analyzed 109 samples to establish the sensitivity and specificity and are prospectively analyzing positive hits in real time to assess clinical utility and cost-effectiveness. [Results]: Retrospectively, biallelic mutations were identified in 85.3% of the samples and single allele mutations in 7.3%. Samples in which no mutations were detected (7.3%) corresponded to hypothyroidism in half of the cases. In samples with previous genetic diagnosis (n=33), 100% concordance was found and a second mutation was identified in two samples. In the prospective phase, current turnaround time is 9 days. Among15 cystic fibrosis (CF) samples analyzed we have found biallelic mutations in 13% cases, single mutations in 53.3% and no mutations in 33.3%. These data are compatible with the high rate of false positives for CF. [Conclusion]: We have successfully developed an NGS panel that may allow to bypass or redirect confirmatory tests and provide earlier genetic counseling in newborn screening programs.

Resumen del póster presentado a la European Human Genetics Conference, celebrada en Barcelona (España) del 21 al 24 de mayo de 2016.-- et al.

Grant support: RETOS2014/5938/I

Peer reviewed