Cardiac Genetic Predisposition in Sudden Infant Death Syndrome.
J Am Coll Cardiol
; 71(11): 1217-1227, 2018 03 20.
Article
em En
| MEDLINE
| ID: mdl-29544605
ABSTRACT
BACKGROUND:
Sudden infant death syndrome (SIDS) is a leading cause of postneonatal mortality. Genetic heart diseases (GHDs) underlie some cases of SIDS.OBJECTIVES:
This study aimed to determine the spectrum and prevalence of GHD-associated mutations as a potential monogenic basis for SIDS.METHODS:
A cohort of 419 unrelated SIDS cases (257 male; average age 2.7 ± 1.9 months) underwent whole exome sequencing and a targeted analysis of 90 GHD-susceptibility genes. The yield of "potentially informative," ultra-rare variants (minor allele frequency <0.00005) in GHD-associated genes was assessed.RESULTS:
Overall, 53 of 419 (12.6%) SIDS cases had ≥1 "potentially informative," GHD-associated variant. The yield was 14.9% (21 of 141) for mixed-European ancestry cases and 11.5% (32 of 278) for European ancestry SIDS cases. Infants older than 4 months were more likely to host a "potentially informative" GHD-associated variant. There was significant overrepresentation of ultra-rare nonsynonymous variants in European SIDS cases (18 of 278 [6.5%]) versus European control subjects (30 of 973 [3.1%]; p = 0.013) when combining all 4 major cardiac channelopathy genes (KCNQ1, KCNH2, SCN5A, and RYR2). According to the American College of Medical Genetics guidelines, only 18 of 419 (4.3%) SIDS cases hosted a "pathogenic" or "likely pathogenic" variant.CONCLUSIONS:
Less than 15% of more than 400 SIDS cases had a "potentially informative" variant in a GHD-susceptibility gene, predominantly in the 4- to 12-month age group. Only 4.3% of cases possessed immediately clinically actionable variants. Consistent with previous studies, ultra-rare, nonsynonymous variants within the major cardiac channelopathy-associated genes were overrepresented in SIDS cases in infants of European ethnicity. These findings have major implications for the investigation of SIDS cases and families.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Morte Súbita do Lactente
/
Variação Genética
/
Sequenciamento do Exoma
Tipo de estudo:
Guideline
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
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Humans
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Infant
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Male
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Newborn
País/Região como assunto:
Europa
Idioma:
En
Revista:
J Am Coll Cardiol
Ano de publicação:
2018
Tipo de documento:
Article