Accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis

Abstract In sudden unexpected death in infancy cases, postmortem genetic analysis with next-generation sequencing potentially can extract candidate genes associated with sudden death. However, it is difficult to accurately interpret the clinically significant genetic variants. The study aim was to c...

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Autores principales:	Keita Shingu, Takehiko Murase, Takuma Yamamoto, Yuki Abe, Yoriko Shinba, Masahide Mitsuma, Takahiro Umehara, Hiromi Yamashita, Kazuya Ikematsu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7c7c566a7d5e473b91676776584a8379
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spelling	oai:doaj.org-article:7c7c566a7d5e473b91676776584a83792021-11-08T10:54:20ZAccurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis10.1038/s41598-021-00962-82045-2322https://doaj.org/article/7c7c566a7d5e473b91676776584a83792021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00962-8https://doaj.org/toc/2045-2322Abstract In sudden unexpected death in infancy cases, postmortem genetic analysis with next-generation sequencing potentially can extract candidate genes associated with sudden death. However, it is difficult to accurately interpret the clinically significant genetic variants. The study aim was to conduct trio analysis of cases of sudden unexpected death in infancy and their parents to more accurately interpret the clinically significant disease-associated gene variants associated with cause of death. From the TruSight One panel targeting 4813 genes we extracted candidate genetic variants of 66 arrhythmia-, 63 inherited metabolic disease-, 81 mitochondrial disease-, and 6 salt-losing tubulopathy-related genes in 7 cases and determined if they were de novo or parental-derived variants. Thirty-four parental-derived variants and no de novo variants were found, but none appeared to be related to the cause of death. Using trio analysis and an in silico algorithm to analyze all 4813 genes, we identified OBSCN of compound heterozygous and HCCS of hemizygous variants as new candidate genetic variants related to cause of death. Genetic analysis of these deceased infants and their living parents can provide more accurate interpretation of the clinically significant genetic variants than previously possible and help confirm the cause of death.Keita ShinguTakehiko MuraseTakuma YamamotoYuki AbeYoriko ShinbaMasahide MitsumaTakahiro UmeharaHiromi YamashitaKazuya IkematsuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Keita Shingu Takehiko Murase Takuma Yamamoto Yuki Abe Yoriko Shinba Masahide Mitsuma Takahiro Umehara Hiromi Yamashita Kazuya Ikematsu Accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis
description	Abstract In sudden unexpected death in infancy cases, postmortem genetic analysis with next-generation sequencing potentially can extract candidate genes associated with sudden death. However, it is difficult to accurately interpret the clinically significant genetic variants. The study aim was to conduct trio analysis of cases of sudden unexpected death in infancy and their parents to more accurately interpret the clinically significant disease-associated gene variants associated with cause of death. From the TruSight One panel targeting 4813 genes we extracted candidate genetic variants of 66 arrhythmia-, 63 inherited metabolic disease-, 81 mitochondrial disease-, and 6 salt-losing tubulopathy-related genes in 7 cases and determined if they were de novo or parental-derived variants. Thirty-four parental-derived variants and no de novo variants were found, but none appeared to be related to the cause of death. Using trio analysis and an in silico algorithm to analyze all 4813 genes, we identified OBSCN of compound heterozygous and HCCS of hemizygous variants as new candidate genetic variants related to cause of death. Genetic analysis of these deceased infants and their living parents can provide more accurate interpretation of the clinically significant genetic variants than previously possible and help confirm the cause of death.
format	article
author	Keita Shingu Takehiko Murase Takuma Yamamoto Yuki Abe Yoriko Shinba Masahide Mitsuma Takahiro Umehara Hiromi Yamashita Kazuya Ikematsu
author_facet	Keita Shingu Takehiko Murase Takuma Yamamoto Yuki Abe Yoriko Shinba Masahide Mitsuma Takahiro Umehara Hiromi Yamashita Kazuya Ikematsu
author_sort	Keita Shingu
title	Accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis
title_short	Accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis
title_full	Accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis
title_fullStr	Accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis
title_full_unstemmed	Accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis
title_sort	accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7c7c566a7d5e473b91676776584a8379
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Accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis

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