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

doi:10.1186/s13052-017-0418-0

Review

. 2017 Nov 3;43(1):100.

doi: 10.1186/s13052-017-0418-0.

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

Collaborators, Affiliations

Collaborators

their respective Scientific Societies:
Rino Agostiniani, Annamaria Staiano, Antonio Del Vecchio, Giuseppe Banderali, Diego Peroni, Ruggiero Piazzolla, Renato Turra, Elena Bozzola, Davide Vecchio, Giovanni Vitali Rosati, Francesco Macrì, Costantino Romagnoli, Mario De Curtis, Luigi Orfeo, Giovanna Mangili, Fabio Mosca, Vassilios Fanos, Piermichele Paolillo, Francesco Raimondi, Angelo Rizzo, Gaetano Chirico, Luigi Tommaso Corvaglia, Caterina Cacace, Carlo Poggiani, Antonio Alberto Zuppa, Denis Pisano, Daniela Melis, Mario Giuffrè, Maria Teresa Carbone, Marina Macchiaiolo, Luigi Tarani, Angelo Selicorni, Generoso Andria, Domenico Coviello, Mattia Gentile, Paola Ghiorzo, Antonio Novelli, Angela Ragusa, Gioacchino Scarano, Daniela Giardino

Affiliations

¹ Neonatal Intensive Care Unit, Fondazione IRCCS Policlinco San Matteo, Piazzale Golgi, 19, 27100, Pavia, Italy. a.borghesi@smatteo.pv.it.
² Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
³ Pediatric Department, S. Martino Hospital, Belluno, Italy.
⁴ Department of Public Health and Pediatrics, University of Torino, Torino, Italy.
⁵ Rare Diseases and Medical Genetic Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁶ Institute of Genomic Medicine, Università Cattolica Del Sacro Cuore, Fondazione Policlinico A. Gemelli, Rome, Italy.
⁷ Neonatal Intensive Care Unit, Fondazione IRCCS Policlinco San Matteo, Piazzale Golgi, 19, 27100, Pavia, Italy.
⁸ Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁹ Medical Genetics, University of Siena, Siena, Italy.
¹⁰ Operative Unit of Pediatrics and Neonatal Intensive Therapy, Mother and Child Department, University of Palermo, Palermo, Italy.

PMID: 29100554
PMCID: PMC5670717
DOI: 10.1186/s13052-017-0418-0

Review

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

Alessandro Borghesi et al. Ital J Pediatr. 2017.

. 2017 Nov 3;43(1):100.

doi: 10.1186/s13052-017-0418-0.

Collaborators

their respective Scientific Societies:
Rino Agostiniani, Annamaria Staiano, Antonio Del Vecchio, Giuseppe Banderali, Diego Peroni, Ruggiero Piazzolla, Renato Turra, Elena Bozzola, Davide Vecchio, Giovanni Vitali Rosati, Francesco Macrì, Costantino Romagnoli, Mario De Curtis, Luigi Orfeo, Giovanna Mangili, Fabio Mosca, Vassilios Fanos, Piermichele Paolillo, Francesco Raimondi, Angelo Rizzo, Gaetano Chirico, Luigi Tommaso Corvaglia, Caterina Cacace, Carlo Poggiani, Antonio Alberto Zuppa, Denis Pisano, Daniela Melis, Mario Giuffrè, Maria Teresa Carbone, Marina Macchiaiolo, Luigi Tarani, Angelo Selicorni, Generoso Andria, Domenico Coviello, Mattia Gentile, Paola Ghiorzo, Antonio Novelli, Angela Ragusa, Gioacchino Scarano, Daniela Giardino

Affiliations

¹ Neonatal Intensive Care Unit, Fondazione IRCCS Policlinco San Matteo, Piazzale Golgi, 19, 27100, Pavia, Italy. a.borghesi@smatteo.pv.it.
² Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
³ Pediatric Department, S. Martino Hospital, Belluno, Italy.
⁴ Department of Public Health and Pediatrics, University of Torino, Torino, Italy.
⁵ Rare Diseases and Medical Genetic Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁶ Institute of Genomic Medicine, Università Cattolica Del Sacro Cuore, Fondazione Policlinico A. Gemelli, Rome, Italy.
⁷ Neonatal Intensive Care Unit, Fondazione IRCCS Policlinco San Matteo, Piazzale Golgi, 19, 27100, Pavia, Italy.
⁸ Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
⁹ Medical Genetics, University of Siena, Siena, Italy.
¹⁰ Operative Unit of Pediatrics and Neonatal Intensive Therapy, Mother and Child Department, University of Palermo, Palermo, Italy.

PMID: 29100554
PMCID: PMC5670717
DOI: 10.1186/s13052-017-0418-0

Abstract

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.

Keywords: Diagnosis; Genetic; Genome; Mendelian; NICU; Neonatal intensive care unit; Neonate; WES; WGS; Whole-exome sequencing.

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Conflict of interest statement

Authors’ information

The respective Scientific Societies of the authors of this paper are as follows: Italian Society of Pediatrics (SIP), Italian Society of Neonatology (SIN), Italian Society of Pediatric Genetic Diseases and Congenital Disabilities (SIMGePed), and Italian Society of Human Genetics (SIGU).

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Diagnostic algorithm for genetic testing in the critically ill newborn infant

See this image and copyright information in PMC

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References

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1. Tetreault M, Bareke E, Nadaf J, Alirezaie N, Majewski J. Whole-exome sequencing as a diagnostic tool: current challenges and future opportunities. Expert Rev Mol Diagn. 2015;15:749–760. - PubMed
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[1] Frebourg T. The challenge for the next generation of medical geneticists. Hum Mutat. 2014;35:909–911. doi: 10.1002/humu.22592. - DOI - PubMed

[2] Frebourg T. The challenge for the next generation of medical geneticists. Hum Mutat. 2014;35:909–911. doi: 10.1002/humu.22592. - DOI - PubMed

[3] Tetreault M, Bareke E, Nadaf J, Alirezaie N, Majewski J. Whole-exome sequencing as a diagnostic tool: current challenges and future opportunities. Expert Rev Mol Diagn. 2015;15:749–760. - PubMed

[4] Tetreault M, Bareke E, Nadaf J, Alirezaie N, Majewski J. Whole-exome sequencing as a diagnostic tool: current challenges and future opportunities. Expert Rev Mol Diagn. 2015;15:749–760. - PubMed

[5] OMIM Gene Map Statistics. http://www.omim.org/statistics/geneMap. Accessed 5 July, 2017.

[6] OMIM Gene Map Statistics. http://www.omim.org/statistics/geneMap. Accessed 5 July, 2017.

[7] Phimister EG, Feero WG, Guttmacher AE. Realizing genomic medicine. N Engl J Med. 2012;366:757–759. doi: 10.1056/NEJMe1200749. - DOI - PubMed

[8] Phimister EG, Feero WG, Guttmacher AE. Realizing genomic medicine. N Engl J Med. 2012;366:757–759. doi: 10.1056/NEJMe1200749. - DOI - PubMed

[9] Saunders CJ, Miller NA, Soden SE, Dinwiddie DL, Noll A, Alnadi NA, Andraws N, Patterson ML, Krivohlavek LA, Fellis J, et al. Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units. Sci Transl Med. 2012;4:154ra135. doi: 10.1126/scitranslmed.3004041. - DOI - PMC - PubMed

[10] Saunders CJ, Miller NA, Soden SE, Dinwiddie DL, Noll A, Alnadi NA, Andraws N, Patterson ML, Krivohlavek LA, Fellis J, et al. Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units. Sci Transl Med. 2012;4:154ra135. doi: 10.1126/scitranslmed.3004041. - DOI - PMC - PubMed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Authors’ information

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

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Cited by

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

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Medical

Research Materials