Precision medicine in rare diseases: What is next?

Abstract

Molecular diagnostics is a cornerstone of modern precision medicine, broadly understood as tailoring an individual's treatment, follow‐up, and care based on molecular data. In rare diseases (RDs), molecular diagnoses reveal valuable information about the cause of symptoms, disease progression, familial risk, and in certain cases, unlock access to targeted therapies. Due to decreasing DNA sequencing costs, genome sequencing (GS) is emerging as the primary method for precision diagnostics in RDs. Several ongoing European initiatives for precision medicine have chosen GS as their method of choice. Recent research supports the role for GS as first‐line genetic investigation in individuals with suspected RD, due to its improved diagnostic yield compared to other methods. Moreover, GS can detect a broad range of genetic aberrations including those in noncoding regions, producing comprehensive data that can be periodically reanalyzed for years to come when further evidence emerges. Indeed, targeted drug development and repurposing of medicines can be accelerated as more individuals with RDs receive a molecular diagnosis. Multidisciplinary teams in which clinical specialists collaborate with geneticists, genomics education of professionals and the public, and dialogue with patient advocacy groups are essential elements for the integration of precision medicine into clinical practice worldwide. It is also paramount that large research projects share genetic data and leverage novel technologies to fully diagnose individuals with RDs. In conclusion, GS increases diagnostic yields and is a crucial step toward precision medicine for RDs. Its clinical implementation will enable better patient management, unlock targeted therapies, and guide the development of innovative treatments.

Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors—a nationwide, prospective Swedish study

“…WGS is emerging as the preferred sequencing method for precision diagnostics due to its ability to reliably detect multiple types of variants, including SVs, 15 , 16 , 32 which accounted for 16% of the findings in our cohort. The same advantage with gWGS applies to tumor WGS, also due to the frequency of SVs and gene fusions in childhood cancer.…”

Towards routine long-read sequencing for rare disease: a national pilot study on chromosomal rearrangements

“…A thorough analysis of such events detailing the DNA breakpoints at the nucleotide level is crucial for comprehending the disease-causing and rearrangement-generating mechanisms. This level of understanding is necessary for effective personalized clinical management and genetic counselling (5).…”

Značaj Precizne Medicine I Farmakogenomike U Preventivnoj Pedijatriji

“…Očekuje se bolje razumevanje osnovnih mehanizama po kojima nastaju različite bolesti uključujući i kardiovaskularne, endokrinloške, gastroenterološke, neurološke i dr. Očekuje se unapređenje pristupima prevencije, dijagnostike i lečenja širokog spektra bolesti. (13,14,15,16) Oblast precizne medicine se intenzivno razvija. Podataka ima sve više, informacije se statističkim programima obrađuju, potrebno ih je na precizan način tumačiti i njihova primena je sve više značajna i pristupačna.…”

“…Precizna medicina uključuje i sve druge oblasti genomike, ali komplementarno uključuje i specifične biomarkere, funkcionalne testove i imidžing tehnike. (15,16) U perspektivi se očekuje da će se genetička dijagnostika implementirati u sve grane medicine te će se i povećati značaj precizne medicine. Mogućnosti implementacije precizne medicine najviše se fokusiraju na bolesti kao što su hipertenzija, angina pektoris -stanja sa dijagnostičkom i prognostičkom neizvesnošću i stanja koja su potencijalno Prev Ped, 2024; 10(1-2): 60-64…”

“…Iako postoji uspeh ovakvog preventivnog pristupa, potrebna je kategorizacija podgrupa bolesti analizom fenotipa i genotipa pacijenata, kako bi se povećala uspešnost prevencije i lečenja i najčešćih i retkih bolesti. (11,13,4,15,16) Svaka obolela osoba je jedinstvena i predstavlja "unikat". Tradicionalni koncept pretpostavlja se da pacijenti sa "zajedničkim" znacima i simptomima bolesti dele isti patološki fenotip bolesti i pretpostavlja se da će reagovati slično na slične intervencije (medicinske, proceduralne i/ili bihevioralne).…”