Intersociety policy statement on the use of whole-exome sequencing in the critically ill newborn infant

被引：0
作者：
Alessandro Borghesi
Maria Antonietta Mencarelli
Luigi Memo
Giovanni Battista Ferrero
Andrea Bartuli
Maurizio Genuardi
Mauro Stronati
Alberto Villani
Alessandra Renieri
Giovanni Corsello
机构：
[1] Neonatal Intensive Care Unit,Pediatric Department
[2] Fondazione IRCCS Policlinco San Matteo,Department of Public Health and Pediatrics
[3] Genetica Medica,Rare Diseases and Medical Genetic Unit
[4] Azienda Ospedaliera Universitaria Senese,Pediatric and Infectious Disease Unit
[5] S. Martino Hospital,Medical Genetics
[6] University of Torino,Operative Unit of Pediatrics and Neonatal Intensive Therapy, Mother and Child Department
[7] Bambino Gesù Children’s Hospital,undefined
[8] IRCCS,undefined
[9] Institute of Genomic Medicine,undefined
[10] Università Cattolica Del Sacro Cuore,undefined
[11] Fondazione Policlinico A. Gemelli,undefined
[12] Bambino Gesù Children’s Hospital,undefined
[13] IRCCS,undefined
[14] University of Siena,undefined
[15] University of Palermo,undefined
来源：
Italian Journal of Pediatrics | / 43卷
关键词：
Neonate; Genome; Whole-exome sequencing; WES; WGS; Genetic; Mendelian; NICU; Neonatal intensive care unit; Diagnosis;
D O I：
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摘要：
The rapid advancement of next-generation sequencing (NGS) technology and the decrease in costs for whole-exome sequencing (WES) and whole-genome sequening (WGS), has prompted its clinical application in several fields of medicine. Currently, there are no specific guidelines for the use of NGS in the field of neonatal medicine and in the diagnosis of genetic diseases in critically ill newborn infants. As a consequence, NGS may be underused with reduced diagnostic success rate, or overused, with increased costs for the healthcare system. Most genetic diseases may be already expressed during the neonatal age, but their identification may be complicated by nonspecific presentation, especially in the setting of critical clinical conditions. The differential diagnosis process in the neonatal intensive care unit (NICU) may be time-consuming, uncomfortable for the patient due to repeated sampling, and ineffective in reaching a molecular diagnosis during NICU stay. Serial gene sequencing (Sanger sequencing) may be successful only for conditions for which the clinical phenotype strongly suggests a diagnostic hypothesis and for genetically homogeneous diseases. Newborn screenings with Guthrie cards, which vary from country to country, are designed to only test for a few dozen genetic diseases out of the more than 6000 diseases for which a genetic characterization is available. The use of WES in selected cases in the NICU may overcome these issues. We present an intersociety document that aims to define the best indications for the use of WES in different clinical scenarios in the NICU. We propose that WES is used in the NICU for critically ill newborn infants when an early diagnosis is desirable to guide the clinical management during NICU stay, when a strong hypothesis cannot be formulated based on the clinical phenotype or the disease is genetically heterogeneous, and when specific non-genetic laboratory tests are not available. The use of WES may reduce the time for diagnosis in infants during NICU stay and may eventually result in cost-effectiveness.
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