Intensive Care Unit Clinical Trial
— REUNIROfficial title:
Fast Exome for Diagnosis of Congenital Conditions in Infants Under 12 Months of Age Hospitalized in Intensive Care Unit
NCT number | NCT03831035 |
Other study ID # | RECHMPL17_0387 |
Secondary ID | |
Status | Completed |
Phase | |
First received | |
Last updated | |
Start date | April 8, 2019 |
Est. completion date | June 8, 2022 |
Verified date | November 2023 |
Source | University Hospital, Montpellier |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
An early diagnosis of congenital malformations and suspected genetic conditions in critically ill infants is essential to perform specific adapted care, prevention, and give proper genetic counseling. However, etiologies are various and each of them is individually very rare. Thanks to next-generation sequencing technologies, diagnosis time frames have drastically decreased and the investigators have observed an increase in diagnosis yields. This study aims to evaluate the feasibility of fast trio exome sequencing (less than 16 days between informed consent signature and the consultation for results to the parents) in infants under the age of 12 months hospitalized in Intensive Care Unit (ICU).
Status | Completed |
Enrollment | 45 |
Est. completion date | June 8, 2022 |
Est. primary completion date | June 8, 2022 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 1 Day to 12 Months |
Eligibility | Inclusion Criteria: - Infant aged under 12 months , hospitalized in the ICU. - Infant with multiple congenital malformations or neurological symptoms for which a genetic origin is suspected but undiagnosed genetically. - Infant for whom both biological parents have given consent for the study, genetic analysis for themselves anf their child. - Infant and parents registered in the French National health service Exclusion Criteria: - Absence of one or both parental sample. - Precise genetic diagnosis made pre- or post-natally with chromosomal (I.e : Down syndrome), Sanger (i.e : infantile spinal amyotrophia) methylation (i.e : Prader-Willi syndrome) or triplet amplification (I.e : neonatal Steinert myotonia) studies. - Strong clinical evidence for a with chromosomal (I.e : Down syndrome), Sanger (i.e : infantile spinal amyotrophia) methylation (i.e : Prader-Willi syndrome) or triplet amplification (I.e : neonatal Steinert myotonia) studies. - Impossibility for one or both parents to give his or her consent |
Country | Name | City | State |
---|---|---|---|
France | Medical genetics Arnaud de Villeneuve | Montpellier | Hérault |
Lead Sponsor | Collaborator |
---|---|
University Hospital, Montpellier |
France,
Acikalin A, Bagir EK, Torun G, Ates BT, Erdogan S, Uguz A, Ergin M, Buyukkurt S, Ozgunen FT, Tunali N, Gumurdulu D. Perinatal autopsy evaluation of 2150 autopsies in the Cukurova region of Turkey. Turk Patoloji Derg. 2014;30(3):189-94. doi: 10.5146/tjpath.2014.01266. — View Citation
Baird PA, Anderson TW, Newcombe HB, Lowry RB. Genetic disorders in children and young adults: a population study. Am J Hum Genet. 1988 May;42(5):677-93. — View Citation
Bonnet D. [Genetics of congenital heart diseases]. Presse Med. 2017 Jun;46(6 Pt 1):612-619. doi: 10.1016/j.lpm.2017.05.014. Epub 2017 Jun 2. French. — View Citation
Cunniff C, Carmack JL, Kirby RS, Fiser DH. Contribution of heritable disorders to mortality in the pediatric intensive care unit. Pediatrics. 1995 May;95(5):678-81. — View Citation
Dhiman V. Molecular Genetics of Epilepsy: A Clinician's Perspective. Ann Indian Acad Neurol. 2017 Apr-Jun;20(2):96-102. doi: 10.4103/aian.AIAN_447_16. — View Citation
FitzPatrick DR, Skeoch CH, Tolmie JL. Genetic aspects of admissions to a paediatric intensive care unit. Arch Dis Child. 1991 May;66(5):639-41. doi: 10.1136/adc.66.5.639. — View Citation
Gilissen C, Hoischen A, Brunner HG, Veltman JA. Unlocking Mendelian disease using exome sequencing. Genome Biol. 2011 Sep 14;12(9):228. doi: 10.1186/gb-2011-12-9-228. — View Citation
Grandemange S, Sanchez E, Louis-Plence P, Tran Mau-Them F, Bessis D, Coubes C, Frouin E, Seyger M, Girard M, Puechberty J, Costes V, Rodiere M, Carbasse A, Jeziorski E, Portales P, Sarrabay G, Mondain M, Jorgensen C, Apparailly F, Hoppenreijs E, Touitou I, Genevieve D. A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis). Ann Rheum Dis. 2017 Jul;76(7):1191-1198. doi: 10.1136/annrheumdis-2016-210021. Epub 2016 Dec 13. — View Citation
Hack M, Taylor HG, Drotar D, Schluchter M, Cartar L, Andreias L, Wilson-Costello D, Klein N. Chronic conditions, functional limitations, and special health care needs of school-aged children born with extremely low-birth-weight in the 1990s. JAMA. 2005 Jul 20;294(3):318-25. doi: 10.1001/jama.294.3.318. — View Citation
Hildreth A, Wigby K, Chowdhury S, Nahas S, Barea J, Ordonez P, Batalov S, Dimmock D, Kingsmore S; RCIGM Investigators. Rapid whole-genome sequencing identifies a novel homozygous NPC1 variant associated with Niemann-Pick type C1 disease in a 7-week-old ma — View Citation
Kingsmore SF, Petrikin J, Willig LK, Guest E. Emergency medical genomes: a breakthrough application of precision medicine. Genome Med. 2015 Jul 30;7(1):82. doi: 10.1186/s13073-015-0201-z. eCollection 2015. — View Citation
Lalani SR. Current Genetic Testing Tools in Neonatal Medicine. Pediatr Neonatol. 2017 Apr;58(2):111-121. doi: 10.1016/j.pedneo.2016.07.002. Epub 2016 Sep 28. — View Citation
Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, Das K, Toy T, Harry B, Yourshaw M, Fox M, Fogel BL, Martinez-Agosto JA, Wong DA, Chang VY, Shieh PB, Palmer CG, Dipple KM, Grody WW, Vilain E, Nelson SF. Clinical exome sequencing for — View Citation
McCandless SE, Brunger JW, Cassidy SB. The burden of genetic disease on inpatient care in a children's hospital. Am J Hum Genet. 2004 Jan;74(1):121-7. doi: 10.1086/381053. Epub 2003 Dec 12. Erratum In: Am J Hum Genet. 2004 Apr;74(4):788. — View Citation
Musante L, Ropers HH. Genetics of recessive cognitive disorders. Trends Genet. 2014 Jan;30(1):32-9. doi: 10.1016/j.tig.2013.09.008. Epub 2013 Oct 28. — View Citation
Pabinger S, Dander A, Fischer M, Snajder R, Sperk M, Efremova M, Krabichler B, Speicher MR, Zschocke J, Trajanoski Z. A survey of tools for variant analysis of next-generation genome sequencing data. Brief Bioinform. 2014 Mar;15(2):256-78. doi: 10.1093/bib/bbs086. Epub 2013 Jan 21. — View Citation
Packer JS, Maxwell EK, O'Dushlaine C, Lopez AE, Dewey FE, Chernomorsky R, Baras A, Overton JD, Habegger L, Reid JG. CLAMMS: a scalable algorithm for calling common and rare copy number variants from exome sequencing data. Bioinformatics. 2016 Jan 1;32(1):133-5. doi: 10.1093/bioinformatics/btv547. Epub 2015 Sep 17. — View Citation
Petrikin JE, Willig LK, Smith LD, Kingsmore SF. Rapid whole genome sequencing and precision neonatology. Semin Perinatol. 2015 Dec;39(8):623-31. doi: 10.1053/j.semperi.2015.09.009. Epub 2015 Oct 29. — View Citation
Reardon S. Fast genetic sequencing saves newborn lives. Nature. 2014 Oct 2;514(7520):13-4. doi: 10.1038/514013a. No abstract available. — View Citation
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5. — View Citation
Saunders CJ, Miller NA, Soden SE, Dinwiddie DL, Noll A, Alnadi NA, Andraws N, Patterson ML, Krivohlavek LA, Fellis J, Humphray S, Saffrey P, Kingsbury Z, Weir JC, Betley J, Grocock RJ, Margulies EH, Farrow EG, Artman M, Safina NP, Petrikin JE, Hall KP, Ki — View Citation
Smith LD, Willig LK, Kingsmore SF. Whole-Exome Sequencing and Whole-Genome Sequencing in Critically Ill Neonates Suspected to Have Single-Gene Disorders. Cold Spring Harb Perspect Med. 2015 Dec 18;6(2):a023168. doi: 10.1101/cshperspect.a023168. — View Citation
Soden SE, Saunders CJ, Willig LK, Farrow EG, Smith LD, Petrikin JE, LePichon JB, Miller NA, Thiffault I, Dinwiddie DL, Twist G, Noll A, Heese BA, Zellmer L, Atherton AM, Abdelmoity AT, Safina N, Nyp SS, Zuccarelli B, Larson IA, Modrcin A, Herd S, Creed M, — View Citation
Thevenon J, Duffourd Y, Masurel-Paulet A, Lefebvre M, Feillet F, El Chehadeh-Djebbar S, St-Onge J, Steinmetz A, Huet F, Chouchane M, Darmency-Stamboul V, Callier P, Thauvin-Robinet C, Faivre L, Riviere JB. Diagnostic odyssey in severe neurodevelopmental d — View Citation
Van der Auwera GA, Carneiro MO, Hartl C, Poplin R, Del Angel G, Levy-Moonshine A, Jordan T, Shakir K, Roazen D, Thibault J, Banks E, Garimella KV, Altshuler D, Gabriel S, DePristo MA. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr Protoc Bioinformatics. 2013;43(1110):11.10.1-11.10.33. doi: 10.1002/0471250953.bi1110s43. — View Citation
Vissers LE, Gilissen C, Veltman JA. Genetic studies in intellectual disability and related disorders. Nat Rev Genet. 2016 Jan;17(1):9-18. doi: 10.1038/nrg3999. Epub 2015 Oct 27. — View Citation
Willig LK, Petrikin JE, Smith LD, Saunders CJ, Thiffault I, Miller NA, Soden SE, Cakici JA, Herd SM, Twist G, Noll A, Creed M, Alba PM, Carpenter SL, Clements MA, Fischer RT, Hays JA, Kilbride H, McDonough RJ, Rosterman JL, Tsai SL, Zellmer L, Farrow EG, — View Citation
Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM. Clinical whole-exome — View Citation
Zlotogora J, Shalev SA. The consequences of consanguinity on the rates of malformations and major medical conditions at birth and in early childhood in inbred populations. Am J Med Genet A. 2010 Aug;152A(8):2023-8. doi: 10.1002/ajmg.a.33537. — View Citation
* Note: There are 29 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Yield of exome results given to the family before 16 days | number of days between the collect sample and results | 16 days maximum after inclusion | |
Secondary | Duration of each step until the results (the analytical step, the bioinformatic step, the interpretation step). | number of days between the collect sample and results | 16 days maximum after inclusion | |
Secondary | Diagnosis yield : identification of the etiology | number of days between the collect sample and diagnostic confirmation | 3 months | |
Secondary | Adjustment of medical care allowed by the exome diagnosis | Any additions or deletions of a diagnostic exam, medical care specific to the diagnosed pathology or screening of a known complication | 16 days maximum after inclusion | |
Secondary | Quantity of blood necessary to achieve diagnosis | blood volume necessary to achieve diagnosis | 16 days maximum after inclusion | |
Secondary | Quantity of blood necessary to achieve diagnosis | number of samples necessary to achieve diagnosis | 16 days maximum after inclusion | |
Secondary | duration of hospital stay in the year following inclusion | number of days of hospital stay in the year | a year after inclusion | |
Secondary | number of medical consultations in the year following inclusion | number of medical consultations in the year | a year after inclusion |
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