Noncardiac genetic predisposition in sudden infant death syndrome.
Alleles
Autopsy
Case-Control Studies
Ethnicity
/ genetics
Exome
Female
Gene Frequency
/ genetics
Genetic Predisposition to Disease
/ genetics
Genetic Variation
/ genetics
Humans
Infant
Infant, Newborn
Male
Mutation
Sudden Infant Death
/ genetics
United Kingdom
United States
White People
/ genetics
Exome Sequencing
Genetics
exome sequencing
molecular autopsy
sudden infant death syndrome
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
18
04
2018
accepted:
28
06
2018
pubmed:
25
8
2018
medline:
16
7
2019
entrez:
25
8
2018
Statut:
ppublish
Résumé
Sudden infant death syndrome (SIDS) is the commonest cause of sudden death of an infant; however, the genetic basis remains poorly understood. We aimed to identify noncardiac genes underpinning SIDS and determine their prevalence compared with ethnically matched controls. Using exome sequencing we assessed the yield of ultrarare nonsynonymous variants (minor allele frequency [MAF] ≤0.00005, dominant model; MAF ≤0.01, recessive model) in 278 European SIDS cases (62% male; average age =2.7 ± 2 months) versus 973 European controls across 61 noncardiac SIDS-susceptibility genes. The variants were classified according to American College of Medical Genetics and Genomics criteria. Case-control, gene-collapsing analysis was performed in eight candidate biological pathways previously implicated in SIDS pathogenesis. Overall 43/278 SIDS cases harbored an ultrarare single-nucleotide variant compared with 114/973 controls (15.5 vs. 11.7%, p=0.10). Only 2/61 noncardiac genes were significantly overrepresented in cases compared with controls (ECE1, 3/278 [1%] vs. 1/973 [0.1%] p=0.036; SLC6A4, 2/278 [0.7%] vs. 1/973 [0.1%] p=0.049). There was no difference in yield of pathogenic or likely pathogenic variants between cases and controls (1/278 [0.36%] vs. 4/973 [0.41%]; p=1.0). Gene-collapsing analysis did not identify any specific biological pathways to be significantly associated with SIDS. A monogenic basis for SIDS amongst the previously implicated noncardiac genes and their encoded biological pathways is negligible.
Identifiants
pubmed: 30139991
doi: 10.1038/s41436-018-0131-4
pii: S1098-3600(21)01036-4
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
641-649Subventions
Organisme : NICHD NIH HHS
ID : R01 HD042569
Pays : United States
Organisme : British Heart Foundation
ID : FS/13/78/30520
Pays : United Kingdom
Références
Krous HF, Beckwith JB, Byard RW, et al. Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach. Pediatrics. 2004;114:234–238.
doi: 10.1542/peds.114.1.234
Kinney HC, Richerson GB, Dymecki SM, et al. The brainstem and serotonin in the sudden infant death syndrome. Annu Rev Pathol. 2009;4:517–550.
doi: 10.1146/annurev.pathol.4.110807.092322
Moon RY, Horne RS, Hauck FR. Sudden infant death syndrome. Lancet. 2007;370:1578–1587.
doi: 10.1016/S0140-6736(07)61662-6
Matthews TJ, MacDorman MF. Infant mortality statistics from the 2010 period linked birth/infant death data set. Natl Vital Stat Rep. 2013;62:1–26.
pubmed: 24735562
Patel V. Unexplained deaths in infancy, England and Wales: 2015. 2015. http://www.ons.gov.uk/peoplepopulationandcommunity/birthdeathsandmarriages/death/bulletins/unexplaineddeathsininfancyenglandandwales/2015 . Accessed 4 May 2018.
Development NIoCHaH. From cells to selves: SIDS strategic plan. NICHD. 2000.
Filiano JJ, Kinney HC. A perspective on neuropathologic findings in victims of the sudden infant death syndrome: the triple-risk model. Biol Neonate. 1994;65:194–197.
doi: 10.1159/000244052
Salomonis N. Systems-level perspective of sudden infant death syndrome. Pediatr Res. 2014;76:220–229.
doi: 10.1038/pr.2014.90
Schwartz PJ. Cardiac sympathetic innervation and the sudden infant death syndrome. A possible pathogenetic link. Am J Med. 1976;60:167–172.
doi: 10.1016/0002-9343(76)90425-3
Guntheroth WG. Theories of cardiovascular causes in sudden infant death syndrome. J Am Coll Cardiol. 1989;14:443–447.
doi: 10.1016/0735-1097(89)90200-3
Yun AJ, Lee PY. Sudden death among infants and adults: companion disorders of maladaptive sympathetic bias. Med Hypotheses. 2004;62:857–860.
doi: 10.1016/j.mehy.2003.11.014
Weese-Mayer DE, Ackerman MJ, Marazita ML, et al. Sudden infant death syndrome: review of implicated genetic factors. Am J Med Genet A. 2007;143A:771–788.
doi: 10.1002/ajmg.a.31722
Van Norstrand DW, Ackerman MJ. Genomic risk factors in sudden infant death syndrome. Genome Med. 2010;2:86.
doi: 10.1186/gm207
Ferrante L, Rognum TO, Vege A, et al. Altered gene expression and possible immunodeficiency in cases of sudden infant death syndrome. Pediatr Res. 2016;80:77–84.
doi: 10.1038/pr.2016.45
Tester DJ, Wong LC, Chanana P, et al. Cardiac genetic predisposition in sudden infant death syndrome. J Am Coll Cardiol. In press.
Ruark E, Münz M, Renwick A, et al. The ICR1000 UK exome series: a resource of gene variation in an outbred population [version 1; referees: 3 approved]. Vol 4 2015.
Cutz E. Whole exome sequencing reveals CLCNKB mutations in a case of sudden unexpected infant death. Pediatr Dev Pathol. 2015;18:339–340.
doi: 10.2350/15-05-1639-LET.1
Fard D, Laer K, Rothamel T, et al. Candidate gene variants of the immune system and sudden infant death syndrome. Int J Legal Med. 2016;130:1025–1033.
doi: 10.1007/s00414-016-1347-y
Laer K, Dork T, Vennemann M, Rothamel T, Klintschar M. Polymorphisms in genes of respiratory control and sudden infant death syndrome. Int J Legal Med. 2015;129:977–984.
doi: 10.1007/s00414-015-1232-0
Lahrouchi N, Lodder EM, Mansouri M, et al. Exome sequencing identifies primary carnitine deficiency in a family with cardiomyopathy and sudden death. Eur J Hum Genet. 2017;25:783–787.
doi: 10.1038/ejhg.2017.22
Yamamoto T, Tanaka H, Emoto Y, et al. Carnitine palmitoyltransferase 2 gene polymorphism is a genetic risk factor for sudden unexpected death in infancy. Brain Dev. 2014;36:479–483.
doi: 10.1016/j.braindev.2013.07.011
Richards S, Aziz N, Bale S, et al. 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;17:405–424.
doi: 10.1038/gim.2015.30
Li Q, Wang K. InterVar: clinical interpretation of genetic variants by the 2015 ACMG-AMP guidelines. Am J Hum Genet . 2017;100:267–280.
doi: 10.1016/j.ajhg.2017.01.004
Kircher M, Witten DM, Jain P, O’Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014;46:310–315.
doi: 10.1038/ng.2892
Frigeni M, Balakrishnan B, Yin X, et al. Functional and molecular studies in primary carnitine deficiency. Hum Mutat. 2017;38:1684–1699.
doi: 10.1002/humu.23315
Lemke JR, Geider K, Helbig KL, et al. Delineating the GRIN1 phenotypic spectrum: a distinct genetic NMDA receptor encephalopathy. Neurology. 2016;86:2171–2178.
doi: 10.1212/WNL.0000000000002740
Fry AE, Fawcett KA, Zelnik N, et al. De novo mutations in GRIN1 cause extensive bilateral polymicrogyria. Brain 2018.
Olpin SE, Clark S, Andresen BS, et al. Biochemical, clinical and molecular findings in LCHAD and general mitochondrial trifunctional protein deficiency. J Inherit Metab Dis. 2005;28:533–544.
doi: 10.1007/s10545-005-0533-8
Hofstra RM, Valdenaire O, Arch E, et al. A loss-of-function mutation in the endothelin-converting enzyme 1 (ECE-1) associated with Hirschsprung disease, cardiac defects, and autonomic dysfunction. Am J Hum Genet. 1999;64:304–308.
doi: 10.1086/302184
Weese-Mayer DE, Berry-Kravis EM, Zhou L, et al. Sudden infant death syndrome: case-control frequency differences at genes pertinent to early autonomic nervous system embryologic development. Pediatr Res. 2004;56:391–395.
doi: 10.1203/01.PDR.0000136285.91048.4A
Weese-Mayer DE, Berry-Kravis EM, Maher BS, Silvestri JM, Curran ME, Marazita ML. Sudden infant death syndrome: association with a promoter polymorphism of the serotonin transporter gene. Am J Med Genet A. 2003;117A:268–274.
doi: 10.1002/ajmg.a.20005
Filonzi L, Magnani C, Nosetti L, et al. Serotonin transporter role in identifying similarities between SIDS and idiopathic ALTE. Pediatrics. 2012;130:e138–144.
doi: 10.1542/peds.2011-3331
Mannikko. RWL, Tester. D, Thor MG, et al. Dysfunction of the skeletal muscle gated sodium channel in sudden infant death syndrome. Lancet. 2018;391:1483–1492.
doi: 10.1016/S0140-6736(18)30021-7
Brownstein CA, Goldstein RD, Thompson CH, et al. SCN1A variants associated with sudden infant death syndrome. Epilepsia. 2018;59:e56–e62.
doi: 10.1111/epi.14055