Noncardiac genetic predisposition in sudden infant death syndrome.
Genet Med
; 21(3): 641-649, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30139991
ABSTRACT
PURPOSE:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
A monogenic basis for SIDS amongst the previously implicated noncardiac genes and their encoded biological pathways is negligible.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Muerte Súbita del Lactante
Tipo de estudio:
Observational_studies
/
Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Infant
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Male
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Newborn
País/Región como asunto:
America do norte
/
Europa
Idioma:
En
Revista:
Genet Med
Asunto de la revista:
GENETICA MEDICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Reino Unido