Avi Fellner1,2, Noa Ruhrman-Shahar3,4, Naama Orenstein4,5, Gabriel Lidzbarsky3, Alan R Shuldiner6, Claudia Gonzaga-Jauregui6, Hadar Brown-Shalev3, Ofir Hagari-Bechar3, Lily Bazak3, Lina Basel-Salmon3,4,7. 1. Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. avi.fellner@gmail.com. 2. The Neurology Department, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. avi.fellner@gmail.com. 3. Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. 4. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 5. Pediatric Genetics Clinic, Schneider Children's Medical Center of Israel, Petah Tikva, Israel. 6. Regeneron Genetics Center, Tarrytown, NY, USA. 7. Laboratory of Immunology and Genetics, Felsenstein Medical Research Center, Petah Tikva, Israel.
Abstract
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.
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.
Authors: Sebastian Köhler; N Christine Øien; Orion J Buske; Tudor Groza; Julius O B Jacobsen; Craig McNamara; Nicole Vasilevsky; Leigh C Carmody; J P Gourdine; Michael Gargano; Julie A McMurry; Daniel Danis; Christopher J Mungall; Damian Smedley; Melissa Haendel; Peter N Robinson Journal: Curr Protoc Hum Genet Date: 2019-09
Authors: Nuno Maia; Maria João Nabais Sá; Manuel Melo-Pires; Arjan P M de Brouwer; Paula Jorge Journal: BMC Genomics Date: 2021-12-20 Impact factor: 3.969