Genetically transitional disease: a new concept in genomic medicine

Area of Science:

• Genetics
• Genomic Medicine
• Disease Classification

Background:

• Traditional genetic disease classification (monogenic/polygenic) is insufficient.
• Scientific advancements necessitate a more nuanced approach to genetic disease categorization.

Purpose of the Study:

• To propose and define a new terminology: genetically transitional disease (GTD).
• To establish a new disease nosology based on genetic architecture gradients.
• To discuss the implications of this new classification for precision medicine.

Main Methods:

• Conceptual framework development.
• Literature review and synthesis.
• Definition of GTD and its occurrence scenarios.

Main Results:

• Introduction of genetically transitional disease (GTD) as a distinct category.
• Proposal of a nosology based on four gradients: monogenic, polygenic, GTD, and mixed.
• Identification of four scenarios for GTD occurrence: subsets of Mendelian disease, modifiable monogenic conditions, variable penetrance, and divergent pathologies from mutational spectra.

Conclusions:

• The proposed GTD classification refines our understanding of genetic disease.
• This new nosology offers a framework for improved precision medicine strategies.
• Therapeutic approaches can be tailored to either the molecular cause or the phenotypic presentation within the GTD framework.