The role of phenotype-based search approaches using public online databases in diagnostics of Mendelian disorders

Avi Fellner, Noa Ruhrman-Shahar, Naama Orenstein, Gabriel Lidzbarsky, Alan R. Shuldiner, Claudia Gonzaga-Jauregui, Hadar Brown-Shalev, Ofir Hagari-Bechar, Lily Bazak, Lina Basel-Salmon

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Purpose: To investigate the effectiveness of phenotype-based search approaches using publicly available online databases. Methods: We included consecutively solved cases from our exome database. For each case, the combination of Human Phenotype Ontology terms reported by the referring clinician was used to perform a search in three commonly used databases: OMIM (first 300 results), Phenolyzer (first 300 results), and Mendelian (all 100 results). Results: One hundred cases were included (43 females; mean age: 10 years). The actual molecular diagnosis identified through exome sequencing was not included in the search results of any of the queried databases in 33% of cases. In 85% of cases it was not found within the top five search results. When included, its median rank was 61 (range: 1–295), 21 (1–270), and 29 (1–92) in OMIM, Phenolyzer and Mendelian, respectively. Conclusion: This study demonstrates that, in most cases, phenotype-based search approaches using public online databases is ineffective in providing a probable diagnosis for Mendelian conditions. Genotype-first approach through molecular-guided diagnostics with backward phenotyping may be a more appropriate approach for these disorders, unless a specific diagnosis is considered a priori based on highly unique phenotypic features or a specific facial gestalt.

Original languageEnglish
Pages (from-to)1095-1100
Number of pages6
JournalGenetics in Medicine
Issue number6
StatePublished - Jun 2021
Externally publishedYes

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Publisher Copyright:
© 2021, The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.


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