{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["15"],"submitter":["Akgun-Dogan O"],"pubmed_abstract":["<b>Background:</b> Pediatric patients with undiagnosed conditions, particularly those suspected of having Mendelian genetic disorders, pose a significant challenge in healthcare. This study investigates the diagnostic yield of whole-genome sequencing (WGS) in a pediatric cohort with diverse phenotypes, particularly focusing on the role of clinical expertise in interpreting WGS results. <b>Methods:</b> A retrospective cohort study was conducted at Acibadem University's Maslak Hospital in Istanbul, Turkey, involving pediatric patients (0-18 years) who underwent diagnostic WGS testing. Clinical assessments, family histories, and previous laboratory and imaging studies were analyzed. Variants were classified and interpreted in conjunction with clinical findings. <b>Results:</b> The cohort comprised 172 pediatric patients, aged 0-5 years (62.8%). International patients (28.5%) were from 20 different countries. WGS was used as a first-tier approach in 61.6% of patients. The diagnostic yield of WGS reached 61.0%, enhanced by reclassification of variants of uncertain significance (VUS) through reverse phenotyping by an experienced clinical geneticist. Consanguinity was 18.6% of the overall cohort. Dual diagnoses were carried out for 8.5% of solved patients. <b>Discussion:</b> Our study particularly advocates for the selection of WGS as a first-tier testing approach in infants and children with rare diseases, who were under 5 years of age, thereby potentially shortening the duration of the diagnostic odyssey. The results also emphasize the critical role of a single clinical geneticist's expertise in deep phenotyping and reverse phenotyping, which contributed significantly to the high diagnostic yield."],"journal":["Frontiers in genetics"],"pagination":["1347474"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10978702"],"repository":["biostudies-literature"],"pubmed_title":["Impact of deep phenotyping: high diagnostic yield in a diverse pediatric population of 172 patients through clinical whole-genome sequencing at a single center."],"pmcid":["PMC10978702"],"pubmed_authors":["Akgun-Dogan O","Tuc Bengur E","Bulut AS","Ay B","Alanay Y","Kar E","Bengur FB","Yigit A","Aydin E","Esen FN","Ozkose GS","Ozdemir O","Yesilyurt A"],"additional_accession":[]},"is_claimable":false,"name":"Impact of deep phenotyping: high diagnostic yield in a diverse pediatric population of 172 patients through clinical whole-genome sequencing at a single center.","description":"<b>Background:</b> Pediatric patients with undiagnosed conditions, particularly those suspected of having Mendelian genetic disorders, pose a significant challenge in healthcare. This study investigates the diagnostic yield of whole-genome sequencing (WGS) in a pediatric cohort with diverse phenotypes, particularly focusing on the role of clinical expertise in interpreting WGS results. <b>Methods:</b> A retrospective cohort study was conducted at Acibadem University's Maslak Hospital in Istanbul, Turkey, involving pediatric patients (0-18 years) who underwent diagnostic WGS testing. Clinical assessments, family histories, and previous laboratory and imaging studies were analyzed. Variants were classified and interpreted in conjunction with clinical findings. <b>Results:</b> The cohort comprised 172 pediatric patients, aged 0-5 years (62.8%). International patients (28.5%) were from 20 different countries. WGS was used as a first-tier approach in 61.6% of patients. The diagnostic yield of WGS reached 61.0%, enhanced by reclassification of variants of uncertain significance (VUS) through reverse phenotyping by an experienced clinical geneticist. Consanguinity was 18.6% of the overall cohort. Dual diagnoses were carried out for 8.5% of solved patients. <b>Discussion:</b> Our study particularly advocates for the selection of WGS as a first-tier testing approach in infants and children with rare diseases, who were under 5 years of age, thereby potentially shortening the duration of the diagnostic odyssey. The results also emphasize the critical role of a single clinical geneticist's expertise in deep phenotyping and reverse phenotyping, which contributed significantly to the high diagnostic yield.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024","modification":"2026-05-22T03:10:44.919Z","creation":"2025-04-06T07:46:13.426Z"},"accession":"S-EPMC10978702","cross_references":{"pubmed":["38560291"],"doi":["10.3389/fgene.2024.1347474"]}}