Genetic Determinants of Sudden Unexpected Death in Pediatrics.
Genet Med
; 24(4): 839-850, 2022 04.
Article
en En
| MEDLINE
| ID: mdl-35027292
ABSTRACT
PURPOSE:
This study aimed to evaluate genetic contributions to sudden unexpected death in pediatrics (SUDP).METHODS:
We phenotyped and performed exome sequencing for 352 SUDP cases. We analyzed variants in 294 "SUDP genes" with mechanisms plausibly related to sudden death. In a subset of 73 cases with parental data (trios), we performed exome-wide analyses and conducted cohort-wide burden analyses.RESULTS:
In total, we identified likely contributory variants in 37 of 352 probands (11%). Analysis of SUDP genes identified pathogenic/likely pathogenic variants in 12 of 352 cases (SCN1A, DEPDC5 [2], GABRG2, SCN5A [2], TTN [2], MYBPC3, PLN, TNNI3, and PDHA1) and variants of unknown significance-favor-pathogenic in 17 of 352 cases. Exome-wide analyses of the 73 cases with family data additionally identified 4 de novo pathogenic/likely pathogenic variants (SCN1A [2], ANKRD1, and BRPF1) and 4 de novo variants of unknown significance-favor-pathogenic. Comparing cases with controls, we demonstrated an excess burden of rare damaging SUDP gene variants (odds ratio, 2.94; 95% confidence interval, 2.37-4.21) and of exome-wide de novo variants in the subset of 73 with trio data (odds ratio, 3.13; 95% confidence interval, 1.91-5.16).CONCLUSION:
We provide strong evidence for a role of genetic factors in SUDP, involving both candidate genes and novel genes for SUDP and expanding phenotypes of disease genes not previously associated with sudden death.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pediatría
/
Muerte Súbita
Tipo de estudio:
Prognostic_studies
Límite:
Child
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Child, preschool
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Humans
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Infant
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Newborn
Idioma:
En
Año:
2022
Tipo del documento:
Article