Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration

Abstract Myelomeningocele (MMC) affects one in 1000 newborns annually worldwide and each surviving child faces tremendous lifetime medical and caregiving burdens. Both genetic and environmental factors contribute to disease risk but the mechanism is unclear. This study examined 506 MMC subjects for...

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Autores principales:	K. S. Au, L. Hebert, P. Hillman, C. Baker, M. R. Brown, D.-K. Kim, K. Soldano, M. Garrett, A. Ashley-Koch, S. Lee, J. Gleeson, J. E. Hixson, A. C. Morrison, H. Northrup
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d4a42c6c5b2a44348b13fe3b51742226
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spelling	oai:doaj.org-article:d4a42c6c5b2a44348b13fe3b517422262021-12-02T14:26:47ZHuman myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration10.1038/s41598-021-83058-72045-2322https://doaj.org/article/d4a42c6c5b2a44348b13fe3b517422262021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83058-7https://doaj.org/toc/2045-2322Abstract Myelomeningocele (MMC) affects one in 1000 newborns annually worldwide and each surviving child faces tremendous lifetime medical and caregiving burdens. Both genetic and environmental factors contribute to disease risk but the mechanism is unclear. This study examined 506 MMC subjects for ultra-rare deleterious variants (URDVs, absent in gnomAD v2.1.1 controls that have Combined Annotation Dependent Depletion score ≥ 20) in candidate genes either known to cause abnormal neural tube closure in animals or previously associated with human MMC in the current study cohort. Approximately 70% of the study subjects carried one to nine URDVs among 302 candidate genes. Half of the study subjects carried heterozygous URDVs in multiple genes involved in the structure and/or function of cilium, cytoskeleton, extracellular matrix, WNT signaling, and/or cell migration. Another 20% of the study subjects carried heterozygous URDVs in candidate genes associated with gene transcription regulation, folate metabolism, or glucose metabolism. Presence of URDVs in the candidate genes involving these biological function groups may elevate the risk of developing myelomeningocele in the study cohort.K. S. AuL. HebertP. HillmanC. BakerM. R. BrownD.-K. KimK. SoldanoM. GarrettA. Ashley-KochS. LeeJ. GleesonJ. E. HixsonA. C. MorrisonH. NorthrupNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-21 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q K. S. Au L. Hebert P. Hillman C. Baker M. R. Brown D.-K. Kim K. Soldano M. Garrett A. Ashley-Koch S. Lee J. Gleeson J. E. Hixson A. C. Morrison H. Northrup Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration
description	Abstract Myelomeningocele (MMC) affects one in 1000 newborns annually worldwide and each surviving child faces tremendous lifetime medical and caregiving burdens. Both genetic and environmental factors contribute to disease risk but the mechanism is unclear. This study examined 506 MMC subjects for ultra-rare deleterious variants (URDVs, absent in gnomAD v2.1.1 controls that have Combined Annotation Dependent Depletion score ≥ 20) in candidate genes either known to cause abnormal neural tube closure in animals or previously associated with human MMC in the current study cohort. Approximately 70% of the study subjects carried one to nine URDVs among 302 candidate genes. Half of the study subjects carried heterozygous URDVs in multiple genes involved in the structure and/or function of cilium, cytoskeleton, extracellular matrix, WNT signaling, and/or cell migration. Another 20% of the study subjects carried heterozygous URDVs in candidate genes associated with gene transcription regulation, folate metabolism, or glucose metabolism. Presence of URDVs in the candidate genes involving these biological function groups may elevate the risk of developing myelomeningocele in the study cohort.
format	article
author	K. S. Au L. Hebert P. Hillman C. Baker M. R. Brown D.-K. Kim K. Soldano M. Garrett A. Ashley-Koch S. Lee J. Gleeson J. E. Hixson A. C. Morrison H. Northrup
author_facet	K. S. Au L. Hebert P. Hillman C. Baker M. R. Brown D.-K. Kim K. Soldano M. Garrett A. Ashley-Koch S. Lee J. Gleeson J. E. Hixson A. C. Morrison H. Northrup
author_sort	K. S. Au
title	Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration
title_short	Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration
title_full	Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration
title_fullStr	Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration
title_full_unstemmed	Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration
title_sort	human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, wnt-signaling, ecm, cytoskeleton and cell migration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d4a42c6c5b2a44348b13fe3b51742226
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Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration

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