Human myelomeningocele risk and ultra-rare deleterious variants in genes associated with cilium, WNT-signaling, ECM, cytoskeleton and cell migration.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 02 2021
11 02 2021
Historique:
received:
06
11
2020
accepted:
28
01
2021
entrez:
12
2
2021
pubmed:
13
2
2021
medline:
16
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33574475
doi: 10.1038/s41598-021-83058-7
pii: 10.1038/s41598-021-83058-7
pmc: PMC7878900
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3639Subventions
Organisme : NICHD NIH HHS
ID : P01 HD035946
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD073434
Pays : United States
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