Blood RNA analysis can increase clinical diagnostic rate and resolve variants of uncertain significance.

ABSTRACT:

Purpose

Diagnosis of genetic disorders is hampered by large numbers of variants of uncertain significance (VUSs) identified through next-generation sequencing. Many such variants may disrupt normal RNA splicing. We examined effects on splicing of a large cohort of clinically identified variants and compared performance of bioinformatic splicing prediction tools commonly used in diagnostic laboratories.

Methods

Two hundred fifty-seven variants (coding and noncoding) were referred for analysis across three laboratories. Blood RNA samples underwent targeted reverse transcription polymerase chain reaction (RT-PCR) analysis with Sanger sequencing of PCR products and agarose gel electrophoresis. Seventeen samples also underwent transcriptome-wide RNA sequencing with targeted splic

SUBMITTER: Wai HA 

PROVIDER: S-EPMC7272326 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature