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

Leslie G. Biesecker, Margaret P. Adam, Fowzan S. Alkuraya, Anne R. Amemiya, Michael J. Bamshad, Anita E. Beck, James T. Bennett, Lynne M. Bird, John C. Carey, Brian Chung, Robin D. Clark, Timothy C. Cox, Cynthia Curry, Mary Beth Palko Dinulos, William B. Dobyns, Philip F. Giampietro, Katta M. Girisha, Ian A. Glass, John M. Graham, Karen W. GrippChad R. Haldeman-Englert, Bryan D. Hall, A. Micheil Innes, Jennifer M. Kalish, Kim M. Keppler-Noreuil, Kenjiro Kosaki, Beth A. Kozel, Ghayda M. Mirzaa, John J. Mulvihill, Malgorzata J.M. Nowaczyk, Roberta A. Pagon, Kyle Retterer, Alan F. Rope, Pedro A. Sanchez-Lara, Laurie H. Seaver, Joseph T. Shieh, Anne M. Slavotinek, Andrew K. Sobering, Cathy A. Stevens, David A. Stevenson, Tiong Yang Tan, Wen Hann Tan, Anne C. Tsai, David D. Weaver, Marc S. Williams, Elaine Zackai, Yuri A. Zarate

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8-15
Number of pages8
JournalAmerican Journal of Human Genetics
Volume108
Issue number1
DOIs
StatePublished - Jan 7 2021

Bibliographical note

Funding Information:
The authors thank Robert L. Nussbaum for critical review of a draft of this manuscript. L.G.B. was supported by the National Institutes of Health (NIH) (ZIA HG200388 06). M.P.A. A.R.A. and R.A.P. are supported by a subcontract from Computercraft Corporation to the University of Washington for editing GeneReviews. T.C.C. was supported by NIH R01 DE027879. J.M.K. was supported by Alex's Lemonade Stand Foundation, Damon Runyon Cancer Research Foundation, and NIH K08CA193915. G.M.M. was supported by NIH K08NS092898 and Jordan's Guardian Angels and the Brotman Baty Institute.

Funding Information:
The authors thank Robert L. Nussbaum for critical review of a draft of this manuscript. L.G.B. was supported by the National Institutes of Health (NIH) ( ZIA HG200388 06 ). M.P.A., A.R.A., and R.A.P. are supported by a subcontract from Computercraft Corporation to the University of Washington for editing GeneReviews. T.C.C. was supported by NIH R01 DE027879 . J.M.K. was supported by Alex’s Lemonade Stand Foundation , Damon Runyon Cancer Research Foundation , and NIH K08CA193915 . G.M.M. was supported by NIH K08NS092898 and Jordan’s Guardian Angels and the Brotman Baty Institute .

Publisher Copyright:
© 2020 American Society of Human Genetics

PubMed: MeSH publication types

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

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