The expanding diagnostic toolbox for rare genetic diseases

Area of Science:

• Genomics
• Rare Diseases
• Genetic Diagnostics

Background:

• Genomic technologies have transformed rare genetic disease care, yet over half of patients remain undiagnosed.
• Established methods like targeted, exome, and short-read sequencing have limitations in identifying all disease-causing variants.

Purpose of the Study:

• To highlight emerging genomic and multi-omic technologies for rare disease diagnosis.
• To emphasize the need for clinical awareness of test strengths, limitations, and challenges.
• To advocate for integrative multi-omics approaches and data sharing for improved diagnostic interpretation.

Main Methods:

• Review of current and emerging genomic technologies (long-read sequencing, optical genome mapping).
• Discussion of multi-omic technologies (transcriptome, epigenome, proteome, metabolome) for variant interpretation.
• Analysis of clinical considerations for selecting and interpreting genetic tests.

Main Results:

• Emerging technologies like long-read sequencing and optical genome mapping show promise for identifying complex genetic variants.
• Multi-omic data can enhance the interpretation of genetic variants.
• Effective utilization requires understanding individual technology strengths and limitations.

Conclusions:

• Integrative multi-omics approaches and data sharing are crucial for advancing rare disease diagnostics.
• Improved diagnostic power from established and emerging technologies can significantly benefit patients.
• Addressing remaining challenges is key to realizing the full potential of genomic diagnostics.