Epigenomic Approaches for the Diagnosis of Rare Diseases

Rare diseases affect more than 300 million people worldwide. Diagnosing rare diseases is a major challenge as they have different causes and etiologies. Careful assessment of clinical symptoms often leads to the testing of the most common genetic alterations that could explain the disease. Patients with negative results for these tests frequently undergo whole exome or genome sequencing, leading to the identification of the molecular cause of the disease in 50% of patients at best. Therefore, a significant proportion of patients remain undiagnosed after sequencing their genome. Recently, approaches based on functional aspects of the genome, including transcriptomics and epigenomics, are beginning to emerge. Here, we will review these approaches, including studies that have successfully provided diagnoses for complex undiagnosed cases.

Automated summary

Rare diseases affect over 300 million people worldwide, but diagnosing them remains a major challenge with only a small percentage of patients finding the molecular cause through genetic testing. Therefore, approaches based on functional aspects of the genome are becoming increasingly important.