Despite advances in clinical genetic testing, including the introduction of exome sequencing
(ES), more than 50% of individuals with a suspected Mendelian condition lack a precise …

RNA sequencing (RNA-seq) has emerged as a powerful approach to discover disease-
causing gene regulatory defects in individuals affected by genetically undiagnosed rare …

Background The majority of clinical genetic testing focuses almost exclusively on regions of
the genome that directly encode proteins. The important role of variants in non-coding …

Aberrant splicing is a major cause of genetic disorders but its direct detection in
transcriptomes is limited to clinically accessible tissues such as skin or body fluids. While …

Background Lack of functional evidence hampers variant interpretation, leaving a large
proportion of individuals with a suspected Mendelian disorder without genetic diagnosis …

BACKGROUND Transcriptome sequencing (RNA-seq) improves diagnostic rates in
individuals with suspected Mendelian conditions to varying degrees, primarily by directing …

Aberrant splicing is a major cause of rare diseases. However, its prediction from genome
sequence alone remains in most cases inconclusive. Recently, RNA sequencing has proven …

Purpose Genetic variants causing aberrant premessenger RNA splicing are increasingly
being recognized as causal variants in genetic disorders. In this study, we devise …

Mutations which affect splicing are significant contributors to rare disease, but are frequently
overlooked by diagnostic sequencing pipelines. Greater ascertainment of pathogenic …

Genome sequencing (GS) is a powerful test for the diagnosis of rare genetic disorders.
Although GS can enumerate most non-coding variation, determining which non-coding …