Impact of deep phenotyping: high diagnostic yield in a diverse pediatric population of 172 patients through clinical whole-genome sequencing at a single center

• DOI: 10.3389/fgene.2024.1347474
• Publication Date: 2024-03-15T04:47:35Z
• Authors: Ozlem Akgun-Dogan; Ecenur Tuc Bengur; Beril Ay; Gulsah Sebnem Ozkose; Emre Kar; Fuat Baris Bengur; Aybike S. Bulut; Ayca Yigit; Eylul Aydin; Fatma Nisa Esen; Ozkan Ozdemir; Ahmet Yesilyurt; Yasemin Alanay
• Keywords: Geneticist

Background: 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 whole-genome sequencing (WGS) pediatric cohort diverse phenotypes, focusing on role clinical expertise interpreting WGS results. Methods: A retrospective was conducted at Acibadem University’s Maslak Hospital Istanbul, Turkey, involving (0–18 years) who underwent testing. Clinical assessments, family histories, and previous laboratory imaging studies were analyzed. Variants classified interpreted conjunction findings. Results: The comprised 172 patients, aged 0–5 years (62.8%). International (28.5%) from 20 different countries. used as first-tier approach 61.6% patients. reached 61.0%, enhanced by reclassification variants uncertain significance (VUS) through reverse phenotyping an experienced geneticist. Consanguinity 18.6% overall cohort. Dual diagnoses carried out for 8.5% solved Discussion: Our advocates selection testing infants children rare diseases, under 5 age, thereby potentially shortening duration odyssey. results also emphasize critical single geneticist’s deep phenotyping, which contributed significantly to high yield.