A comprehensive iterative approach is highly effective in diagnosing individuals who are exome negative.

ABSTRACT:

Purpose

Sixty to seventy-five percent of individuals with rare and undiagnosed phenotypes remain undiagnosed after exome sequencing (ES). With standard ES reanalysis resolving 10-15% of the ES negatives, further approaches are necessary to maximize diagnoses in these individuals.

Methods

In 38 ES negative patients an individualized genomic-phenotypic approach was employed utilizing (1) phenotyping; (2) reanalyses of FASTQ files, with innovative bioinformatics; (3) targeted molecular testing; (4) genome sequencing (GS); and (5) conferring of clinical diagnoses when pathognomonic clinical findings occurred.

Results

Certain and highly likely diagnoses were made in 18/38 (47%) individuals, including identifying two new developmental disorders. The majority of diagnoses (>

SUBMITTER: Shashi V 

PROVIDER: S-EPMC6295275 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature