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. 2024 Jul 4:12:1412880.
doi: 10.3389/fped.2024.1412880. eCollection 2024.

Rapid genome sequencing for critically ill infants: an inaugural pilot study from Turkey

Bengisu Guner Yilmaz  1 , Ozlem Akgun-Dogan  2   3   4 , Ozkan Ozdemir  3   5   6 , Bayram Yuksel  7 , Ozden Hatirnaz Ng  3   6 , Kaya Bilguvar  3   8 , Beril Ay  9 , Gulsah Sebnem Ozkose  5 , Eylul Aydin  5 , Ayca Yigit  5 , Aybike Bulut  5 , Fatma Nisa Esen  10 , Serdar Beken  11 , Selma Aktas  11 , Atalay Demirel  11 , Baran Cengiz Arcagok  11 , Ebru Kazanci  11 , İbrahim Bingol  12 , Ozge Umur  12 , Guntulu Sik  12 , Ugur Isik  13 , Melike Ersoy  14 , Ayse Korkmaz  11 , Agop Citak  12 , Adil Mardinoglu  7   15   16 , Ugur Ozbek  3   5   8 , Yasemin Alanay  2   3   5
Affiliations

Rapid genome sequencing for critically ill infants: an inaugural pilot study from Turkey

Bengisu Guner Yilmaz et al. Front Pediatr. .

Abstract

Introduction: Rare and ultra-rare genetic conditions significantly contribute to infant morbidity and mortality, often presenting with atypical features and genetic heterogeneity that complicate management. Rapid genome sequencing (RGS) offers a timely and cost-effective approach to diagnosis, aiding in early clinical management and reducing unnecessary interventions. This pilot study represents the inaugural use of next-generation sequencing (NGS) as a diagnostic instrument for critically ill neonatal and pediatric ICU patients in a Turkish hospital setting.

Methods: Ten infants were enrolled based on predefined inclusion criteria, and trio RGS was performed. The mean age of the participants was 124 days, with congenital abnormalities being the most common indication for testing. Three patients had consanguineous parents. The mean turnaround time from enrollment to delivery of results was 169 h, with a diagnostic yield of 50%.

Results: Three patients received a definitive molecular diagnosis, impacting their clinical management. Two patients benefited from the exclusion of Mendelian conditions, leading to alternative diagnoses.

Discussion: This study demonstrates the feasibility and results of RGS in Turkish hospital settings, emphasizing the importance of timely genetic diagnosis in reducing the diagnostic odyssey for families and improving patient care. Further research is needed to evaluate the cost-effectiveness and applicability of RGS in the Turkish healthcare system for children with diseases of uncertain etiology.

Keywords: critically ill patient; neonatal intensive care unit; pediatric intensive care unit; rapid genome sequencing; trio sequencing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Illustration summarizing the study design from patient selection to management changes. Image conceived using Biorender.com.
Figure 2
Figure 2
Timeline and process flow graph demonstrating each part of the workflow. Image conceived using Biorender.com.
Figure 3
Figure 3
Overall implications of management in the 10 patients and their families. Image conceived using Biorender.com.
See this image and copyright information in PMC

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