Molecular diagnostic approach to rare neurological diseases from a clinician viewpoint.

Abstract

Advancements in sequencing technology have significantly enhanced diagnostic capabilities for rare neurological diseases. This progress in molecular diagnostics can greatly impact clinical management and facilitate the development of personalized treatments for patients with rare neurological diseases. Neurologists with expertise should raise clinical awareness, as phenotyping remains crucial for making a clinical diagnosis, even in the genomics era. They should prioritize different types of genomic tests, considering both the benefits and the limitations inherent to each test. Notably, long-read sequencing is being utilized in cases suspected to involve repeat expansion disorders or complex structural variants. Repeat expansion disorders are highly prevalent in neurological diseases, particularly within the ataxia group. Significant efforts, including periodic reanalysis, data sharing, or integration of genomics with multi-omics studies, should be directed toward cases that remain undiagnosed after standard next-generation sequencing.