Whole-Exome Sequencing in Critically Ill Neonates and Infants: Diagnostic Yield and Predictability of Monogenic Diagnosis

被引：20

作者：

Scholz, Tasja ^{[1
]}

Blohm, Martin Ernst ^{[2
]}

Kortum, Fanny ^{[1
]}

Bierhals, Tatjana ^{[1
]}

Lessel, Davor ^{[1
]}

van der Ven, Amelie T. ^{[1
]}

Lisfeld, Jasmin ^{[1
]}

Herget, Theresia ^{[1
]}

Kloth, Katja ^{[1
]}

Singer, Dominique ^{[2
]}

Perez, Anna ^{[2
]}

Obi, Nadia ^{[3
]}

Johannsen, Jessika ^{[4
]}

Denecke, Jonas ^{[4
]}

Santer, Rene ^{[4
]}

Kubisch, Christian ^{[1
]}

Deindl, Philipp ^{[2
]}

Hempel, Maja ^{[1
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Dept Pediat, Div Neonatol & Pediat Intens Care, Hamburg, Germany

[3] Univ Med Ctr Hamburg Eppendorf, Dept Med Biometr Epidemiol, Hamburg, Germany

[4] Univ Med Ctr Hamburg Eppendorf, Dept Pediat, Hamburg, Germany

来源：

NEONATOLOGY | 2021年 / 118卷 / 04期

关键词：

Whole-exome sequencing; Neonatal intensive care; Preterm infant; Diagnostic workflow; Genetic diagnostics; PHENOTYPE;

D O I：

10.1159/000516890

中图分类号：

R72 [儿科学];

学科分类号：

100202 ;

摘要：

Introduction: Monogenic diseases play an important role in critically ill neonates and infants treated in the intensive care unit. This study aimed to determine the diagnostic yield of whole-exome sequencing (WES) for monogenic diseases and identify phenotypes more likely associated with a genetic etiology. Methods: From March 2017 to 2020, a comprehensive diagnostic workup including WES in a single academic center was performed in 61 unrelated, critically ill neonates and infants with an unknown underlying disease within the first year of life. We conducted 59 trio-WES, 1 duo-WES, and 1 single-WES analyses. Symptoms were classified according to the Human Phenotype Ontology. Results: The overall molecular genetic diagnostic rate within our cohort was 46% (28/61) and 50% (15/30) in the subgroup of preterm neonates. Identifying the genetic cause of disease facilitates individualized management in the majority of patients. A positive or negative predictive power of specific clinical features for a genetic diagnosis could not be observed. Conclusion: WES is a powerful noninvasive diagnostic tool in critically ill neonates and infants with a high diagnostic rate. We recommend initiating WES as early as possible due to the impact on management and family counseling. Recommendations regarding the clinical utility of WES in critically ill neonates and infants should not be based on the phenotype alone. Here, we present a clinical workflow for the application of WES for critically ill neonates and infants in an interdisciplinary setting.

引用

页码：454 / 461

页数：8

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