A dyadic approach to the delineation of diagnostic entities in clinical genomics

Am J Hum Genet. 2021 Jan 7;108(1):8-15. doi: 10.1016/j.ajhg.2020.11.013.


The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as "GENE-related phenotype descriptor" (e.g., "CFTR-related cystic fibrosis"). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Genetic Diseases, Inborn / diagnosis*
  • Genetic Diseases, Inborn / genetics*
  • Genomics / methods*
  • Genotype
  • Humans
  • Mutation / genetics
  • Phenotype


  • Cystic Fibrosis Transmembrane Conductance Regulator