FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4200478509> ?p ?o ?g. }

• W4200478509 abstract "Sudden unexplained death in childhood (SUDC) is an understudied problem. Whole-exome sequence data from 124 trios (decedent child, living parents) was used to test for excessive de novo mutations (DNMs) in genes involved in cardiac arrhythmias, epilepsy, and other disorders. Among decedents, nonsynonymous DNMs were enriched in genes associated with cardiac and seizure disorders relative to controls (odds ratio = 9.76, P = 2.15 × 10-4). We also found evidence for overtransmission of loss-of-function (LoF) or previously reported pathogenic variants in these same genes from heterozygous carrier parents (11 of 14 transmitted, P = 0.03). We identified a total of 11 SUDC proband genotypes (7 de novo, 1 transmitted parental mosaic, 2 transmitted parental heterozygous, and 1 compound heterozygous) as pathogenic and likely contributory to death, a genetic finding in 8.9% of our cohort. Two genes had recurrent missense DNMs, RYR2 and CACNA1C Both RYR2 mutations are pathogenic (P = 1.7 × 10-7) and were previously studied in mouse models. Both CACNA1C mutations lie within a 104-nt exon (P = 1.0 × 10-7) and result in slowed L-type calcium channel inactivation and lower current density. In total, six pathogenic DNMs can alter calcium-related regulation of cardiomyocyte and neuronal excitability at a submembrane junction, suggesting a pathway conferring susceptibility to sudden death. There was a trend for excess LoF mutations in LoF intolerant genes, where ≥1 nonhealthy sample in denovo-db has a similar variant (odds ratio = 6.73, P = 0.02); additional uncharacterized genetic causes of sudden death in children might be discovered with larger cohorts." @default.
• W4200478509 created "2021-12-31" @default.
• W4200478509 creator A5000731940 @default.
• W4200478509 creator A5005470710 @default.
• W4200478509 creator A5022703708 @default.
• W4200478509 creator A5024558351 @default.
• W4200478509 creator A5028006387 @default.
• W4200478509 creator A5031959056 @default.
• W4200478509 creator A5051109596 @default.
• W4200478509 creator A5052564552 @default.
• W4200478509 creator A5055125250 @default.
• W4200478509 creator A5056299933 @default.
• W4200478509 creator A5057671051 @default.
• W4200478509 creator A5063173199 @default.
• W4200478509 creator A5068110102 @default.
• W4200478509 creator A5070365313 @default.
• W4200478509 date "2021-12-20" @default.
• W4200478509 modified "2023-10-03" @default.
• W4200478509 title "De novo mutations in childhood cases of sudden unexplained death that disrupt intracellular Ca ²⁺ regulation" @default.
• W4200478509 cites W1516382070 @default.
• W4200478509 cites W1533942137 @default.
• W4200478509 cites W1742756123 @default.
• W4200478509 cites W1901036498 @default.
• W4200478509 cites W1905558774 @default.
• W4200478509 cites W1974659994 @default.
• W4200478509 cites W1978819017 @default.
• W4200478509 cites W1981744250 @default.
• W4200478509 cites W2004454757 @default.
• W4200478509 cites W2008627757 @default.
• W4200478509 cites W2011851718 @default.
• W4200478509 cites W2019028325 @default.
• W4200478509 cites W2046969024 @default.
• W4200478509 cites W2049833458 @default.
• W4200478509 cites W2050501047 @default.
• W4200478509 cites W2057150797 @default.
• W4200478509 cites W2064374355 @default.
• W4200478509 cites W2066092841 @default.
• W4200478509 cites W2081524260 @default.
• W4200478509 cites W2102069121 @default.
• W4200478509 cites W2130124702 @default.
• W4200478509 cites W2138773108 @default.
• W4200478509 cites W2139214355 @default.
• W4200478509 cites W2148858864 @default.
• W4200478509 cites W2156198263 @default.
• W4200478509 cites W2160995259 @default.
• W4200478509 cites W2168950294 @default.
• W4200478509 cites W2171090485 @default.
• W4200478509 cites W2256016639 @default.
• W4200478509 cites W2257198171 @default.
• W4200478509 cites W2341636876 @default.
• W4200478509 cites W2413169575 @default.
• W4200478509 cites W2498582720 @default.
• W4200478509 cites W2514744505 @default.
• W4200478509 cites W2517353926 @default.
• W4200478509 cites W2528228681 @default.
• W4200478509 cites W2536017019 @default.
• W4200478509 cites W2554756829 @default.
• W4200478509 cites W2555584998 @default.
• W4200478509 cites W2581649032 @default.
• W4200478509 cites W2587877487 @default.
• W4200478509 cites W2625344977 @default.
• W4200478509 cites W2749242594 @default.
• W4200478509 cites W2751690664 @default.
• W4200478509 cites W2762779950 @default.
• W4200478509 cites W2792146042 @default.
• W4200478509 cites W2803100386 @default.
• W4200478509 cites W2888770928 @default.
• W4200478509 cites W2888986656 @default.
• W4200478509 cites W2892762683 @default.
• W4200478509 cites W2900569176 @default.
• W4200478509 cites W2941974705 @default.
• W4200478509 cites W2947628999 @default.
• W4200478509 cites W2949076809 @default.
• W4200478509 cites W2972329507 @default.
• W4200478509 cites W2987822827 @default.
• W4200478509 cites W3001704276 @default.
• W4200478509 cites W3014628510 @default.
• W4200478509 cites W3029661147 @default.
• W4200478509 cites W3036929104 @default.
• W4200478509 cites W30756424 @default.
• W4200478509 cites W3084707130 @default.
• W4200478509 cites W3097884260 @default.
• W4200478509 cites W3189694098 @default.
• W4200478509 doi "https://doi.org/10.1073/pnas.2115140118" @default.
• W4200478509 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34930847" @default.
• W4200478509 hasPublicationYear "2021" @default.
• W4200478509 type Work @default.
• W4200478509 citedByCount "14" @default.
• W4200478509 countsByYear W42004785092022 @default.
• W4200478509 countsByYear W42004785092023 @default.
• W4200478509 crossrefType "journal-article" @default.
• W4200478509 hasAuthorship W4200478509A5000731940 @default.
• W4200478509 hasAuthorship W4200478509A5005470710 @default.
• W4200478509 hasAuthorship W4200478509A5022703708 @default.
• W4200478509 hasAuthorship W4200478509A5024558351 @default.
• W4200478509 hasAuthorship W4200478509A5028006387 @default.
• W4200478509 hasAuthorship W4200478509A5031959056 @default.
• W4200478509 hasAuthorship W4200478509A5051109596 @default.
• W4200478509 hasAuthorship W4200478509A5052564552 @default.
• W4200478509 hasAuthorship W4200478509A5055125250 @default.

• next