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. 2024 Jun;26(6):101115.
doi: 10.1016/j.gim.2024.101115. Epub 2024 Mar 1.

Exome and genome sequencing in a heterogeneous population of patients with rare disease: Identifying predictors of a diagnosis

Jenna Pucel  1 , Lauren C Briere  2 , Chloe Reuter  3 , Perman Gochyyev  4 ; Undiagnosed Diseases Network; Kimberly LeBlanc  5
Collaborators, Affiliations

Exome and genome sequencing in a heterogeneous population of patients with rare disease: Identifying predictors of a diagnosis

Jenna Pucel et al. Genet Med. 2024 Jun.

Abstract

Purpose: Exome (ES) and genome sequencing (GS) are increasingly being utilized for individuals with rare and undiagnosed diseases; however, guidelines on their use remain limited. This study aimed to identify factors associated with diagnosis by ES and/or GS in a heterogeneous population of patients with rare and undiagnosed diseases.

Methods: In this case control study, we reviewed data from 400 diagnosed and 400 undiagnosed randomly selected participants in the Undiagnosed Diseases Network, all of whom had undergone ES and/or GS. We analyzed factors associated with receiving a diagnosis by ES and/or GS.

Results: Factors associated with a decreased odds of being diagnosed included adult symptom onset, singleton sequencing, and having undergone ES and/or GS before acceptance to the Undiagnosed Diseases Network (48%, 51%, and 32% lower odds, respectively). Factors that increased the odds of being diagnosed by ES and/or GS included having primarily neurological symptoms and having undergone prior chromosomal microarray testing (44% and 59% higher odds, respectively).

Conclusion: We identified several factors that were associated with receiving a diagnosis by ES and/or GS. This will ideally inform the utilization of ES and/or GS and help manage expectations of individuals and families undergoing these tests.

Keywords: Exome sequencing; Genome sequencing; Predictors of a diagnosis; Rare disease; Undiagnosed disease.

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Conflict of interest statement

Conflict of Interest The authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.. Study design.
ES, exome sequencing; GS, genome sequencing; UDN, Undiagnosed Diseases Network; P, pathogenic; LP, likely pathogenic
See this image and copyright information in PMC

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