Expanded carrier screening: Are you prepared?
Dr Gregg is the BL Stalnaker Professor, Chief of Maternal-Fetal Medicine and Director of Obstetrics at UF Health Shands Hospital, University of Florida, Gainesville. He has no conflicts of interest to report in respect to the content of this article.
Next generation sequencing (NGS) technology represents a challenge to traditional prenatal genetic screening for recessive conditions. Specifically, what has been dubbed “expanded carrier screening” (ECS) makes gene-by-gene or a la carte genetic screening menus obsolete. Before the advent of NGS, sequencing was labor-intensive, costly, and slow, and it was difficult to screen large numbers of people for multiple genetic conditions and to evaluate many pathogenic variants (aka mutations) within the same gene. With NGS, genetic information (nucleotides) can be evaluated (sequenced) rapidly and at low cost.1
Two basic principles
The hierarchical approach to carrier screening for single-gene disorders (positive family history followed by racial/ethnic identification) has evolved to include panethnic, multiple-condition screening, using more pathogenic variants. Expanded carrier screening utilizes genetic technology, panels with specific genes and variants as targets or sequencing strategies with results for specific genes whose pathogenic variants are selectively reported. These technologies can be applied using the hierarchical approach or they can be used in a panethnic fashion to identify carriers in those with unsuspecting ancestry or unknown family history. Importantly, when family history for a single gene disorder is positive, ECS may not be the best choice because family-specific and already-identified pathogenic variants may not be included on commercially available screening panels. Genetic counseling by a trained professional should be considered before implementing ECS in cases of a family history of a single-gene disorder. At the heart of ECS is a requirement that patients and providers understand 2 basic principles.