A curated gene list for reporting results of newborn genomic sequencing

作者：Ceyhan Birsoy Ozge; Machini Kalotina; Lebo Matthew S; Yu Tim W; Agrawal Pankaj B; Parad Richard B; Holm Ingrid A; McGuire Amy; Green Robert C; Beggs Alan H; Rehm Heidi L

来源：Genetics in Medicine, 2017, 19(7): 809-818.

DOI：10.1038/gim.2016.193

• clinical validity
• exome sequencing
• gene-disease association
• newborn screening

Purpose: Genomic sequencing (GS) for newborns may enable detection of conditions for which early knowledge can improve health outcomes. One of the major challenges hindering its broader application is the time it takes to assess the clinical relevance of detected variants and the genes they impact so that disease risk is reported appropriately.
Methods: To facilitate rapid interpretation of GS results in newborns, we curated a catalog of genes with putative pediatric relevance for their validity based on the ClinGen clinical validity classification framework criteria, age of onset, penetrance, and mode of inheritance through systematic evaluation of published evidence. Based on these attributes, we classified genes to guide the return of results in the BabySeq Project, a randomized, controlled trial exploring the use of newborn GS (nGS), and used our curated list for the first 15 newborns sequenced in this project.
Results: Here, we present our curated list for 1,514 gene-disease associations. Overall, 954 genes met our criteria for return in nGS. This reference list eliminated manual assessment for 41% of rare variants identified in 15 newborns.
Conclusion: Our list provides a resource that can assist in guiding the interpretive scope of clinical GS for newborns and potentially other populations.

• 出版日期2017-7