Genomic screening of new-born children

Past decade brought rapid advancements of human genetics and human genome analysis. The advent of next generation sequencing (NGS) technology revolutionized the field of rare human disease diagnostics, while technological breakthroughs in the field of genome modification technologies revealed completely new options of rare disease treatment. Genetic therapies where pre-symptomatic patient identification and rapid intervention  are crucial are already changing the clinical approach in treatment of spinal muscular atrophy (onasemnogene abeparvovec – brand name Zolgensma®), and at the same time facilitating rapid adoption of qPCR based SMA (Spinal Muscular Atrophy) screening into national universal new-born screening programs (NBS) worldwide. Considering the increasing number of potential novel gene therapies entering clinical testing, NBS will have to establish rapid response system enabling swift adoption of novel tests when novel therapies become available. It is anticipated that future new-born screening program will involve target gene analysis based on next generation sequencing technology (NGS). There is still no consensus of how exactly the NGS should be introduced into NBS and there is lack of data on population wide introduction of NGS based methods into NBS programs. Several small-scale projects showed that there is significant interest of general population to upgrade NBS programs with advanced genome testing capabilities. Recently (2021) 25mil. EUR was allocated to EU project “Screen4Care” that aims to introduce artificial intelligence into new-born genomic screening to accelerate identification of rare diseases. Slovenia has modern and advanced universal NBS program, utilizing NGS technology as part of confirmatory testing. The Slovenian NBS program is centralized in the home institution of the PI, with all the Slovenian new-borns being tested in this facility. The size of Slovenian new-born population and cutting-edge NBS testing facility makes Slovenia an optimal country to develop basic operational concepts an introduce first pilot universal nation-wide genetic screening NBS program. The aim of this project is to develop laboratory and analytical protocols of new-born genomic screening by next generation sequencing technology, to identify potential weak points and bottlenecks in the process and find suitable solutions and improvements. Additionally, we wish to address social and ethical questions that are important to the nation-wide implementation of NGS genetic screening of new-born children.