Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit

Journal of Clinical Medicine
Robert ŚmigielRafał Płoski

Abstract

Genetic disorders are the leading cause of infant morbidity and mortality. Due to the large number of genetic diseases, molecular and phenotype heterogeneity and often severe course, these diseases remain undiagnosed. In infants with a suspected acute monogenic disease, rapid whole-exome sequencing (R-WES) can be successfully performed. R-WES (singletons) was performed in 18 unrelated infants with a severe and/or progressing disease with the suspicion of genetic origin hospitalized in an Intensive Care Unit (ICU). Blood samples were also collected from the parents. The results from the R-WES were available after 5-14 days. A conclusive genetic diagnosis was obtained in 13 children, corresponding to an overall diagnostic yield of 72.2%. For nine patients, R-WES was used as a first-tier test. Eight patients were diagnosed with inborn errors of metabolism, mainly mitochondrial diseases. In two patients, the disease was possibly caused by variants in genes which so far have not been associated with human disease (NARS1 and DCAF5). R-WES proved to be an effective diagnostic tool for critically ill infants in ICUs suspected of having a genetic disorder. It also should be considered as a first-tier test after precise clinical descript...Continue Reading

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Citations

Mar 30, 2021·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·A Di GiorgioL D'Antiga
May 8, 2021·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Karolina SkalskaBłażej Męczekalski
Jun 3, 2021·Pediatric Transplantation·Charles B ChenKadakkal Radhakrishnan
Aug 28, 2021·American Journal of Medical Genetics. Part a·Małgorzata RydzaniczRafał Płoski

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Methods Mentioned

BETA
exome sequencing
genotyping

Software Mentioned

REVEL
Ensembl VEP
SIFT
DeepVariant
MVP
CAP
MutationTaster
HaplotypeCaller
Varsome
GATK

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