How to proceed after "negative" exome: A review on genetic diagnostics, limitations, challenges, and emerging new multiomics techniques.

ABSTRACT: Exome sequencing (ES) in the clinical setting of inborn metabolic diseases (IMDs) has created tremendous improvement in achieving an accurate and timely molecular diagnosis for a greater number of patients, but it still leaves the majority of patients without a diagnosis. In parallel, (personalized) treatment strategies are increasingly available, but this requires the availability of a molecular diagnosis. IMDs comprise an expanding field with the ongoing identification of novel disease genes and the recognition of multiple inheritance patterns, mosaicism, variable penetrance, and expressivity for known disease genes. The analysis of trio ES is preferred over singleton ES as information on the allelic origin (paternal, maternal, "de novo") reduces the number of variants that require inter

SUBMITTER: Wortmann SB 

PROVIDER: S-EPMC9539960 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature