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Impact of deep phenotyping: high diagnostic yield in a diverse pediatric population of 172 patients through clinical whole-genome sequencing at a single center.
Akgun-Dogan, Ozlem; Tuc Bengur, Ecenur; Ay, Beril; Ozkose, Gulsah Sebnem; Kar, Emre; Bengur, Fuat Baris; Bulut, Aybike S; Yigit, Ayca; Aydin, Eylul; Esen, Fatma Nisa; Ozdemir, Ozkan; Yesilyurt, Ahmet; Alanay, Yasemin.
Afiliación
  • Akgun-Dogan O; Division of Pediatric Genetics, Department of Pediatrics, School of Medicine, Acibadem University, Istanbul, Türkiye.
  • Tuc Bengur E; Rare Diseases and Orphan Drugs Application and Research Center (ACURARE), Acibadem University, Istanbul, Türkiye.
  • Ay B; Department of Genome Studies, Health Sciences Institute, Acibadem University, Istanbul, Türkiye.
  • Ozkose GS; Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States.
  • Kar E; School of Medicine, Acibadem University, Istanbul, Türkiye.
  • Bengur FB; School of Medicine, Acibadem University, Istanbul, Türkiye.
  • Bulut AS; Rare Diseases and Orphan Drugs Application and Research Center (ACURARE), Acibadem University, Istanbul, Türkiye.
  • Yigit A; Department of Genome Studies, Health Sciences Institute, Acibadem University, Istanbul, Türkiye.
  • Aydin E; School of Medicine, Acibadem University, Istanbul, Türkiye.
  • Esen FN; School of Medicine, Acibadem University, Istanbul, Türkiye.
  • Ozdemir O; Rare Diseases and Orphan Drugs Application and Research Center (ACURARE), Acibadem University, Istanbul, Türkiye.
  • Yesilyurt A; Department of Genome Studies, Health Sciences Institute, Acibadem University, Istanbul, Türkiye.
  • Alanay Y; Rare Diseases and Orphan Drugs Application and Research Center (ACURARE), Acibadem University, Istanbul, Türkiye.
Front Genet ; 15: 1347474, 2024.
Article en En | MEDLINE | ID: mdl-38560291
ABSTRACT

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 of whole-genome sequencing (WGS) in a pediatric cohort with diverse phenotypes, particularly focusing on the role of clinical expertise in interpreting WGS results.

Methods:

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.

Results:

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.

Discussion:

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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Genet Año: 2024 Tipo del documento: Article Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Genet Año: 2024 Tipo del documento: Article Pais de publicación: Suiza