Burden of rare deleterious variants in WNT signaling genes among 511 myelomeningocele patients.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
16
06
2020
accepted:
28
08
2020
entrez:
24
9
2020
pubmed:
25
9
2020
medline:
5
11
2020
Statut:
epublish
Résumé
Genes in the noncanonical WNT signaling pathway controlling planar cell polarity have been linked to the neural tube defect myelomeningocele. We hypothesized that some genes in the WNT signaling network have a higher mutational burden in myelomeningocele subjects than in reference subjects in gnomAD. Exome sequencing data from 511 myelomeningocele subjects was obtained in-house and data from 29,940 ethnically matched subjects was provided by version 2 of the publicly available Genome Aggregation Database. To compare mutational burden, we collapsed rare deleterious variants across each of 523 human WNT signaling genes in case and reference populations. Ten WNT signaling genes were disrupted with a higher mutational burden among Mexican American myelomeningocele subjects compared to reference subjects (Fishers exact test, P ≤ 0.05) and seven different genes were disrupted among individuals of European ancestry compared to reference subjects. Gene ontology enrichment analyses indicate that genes disrupted only in the Mexican American population play a role in planar cell polarity whereas genes identified in both populations are important for the regulation of canonical WNT signaling. In summary, evidence for WNT signaling genes that may contribute to myelomeningocele in humans is presented and discussed.
Identifiants
pubmed: 32970752
doi: 10.1371/journal.pone.0239083
pii: PONE-D-20-18473
pmc: PMC7514064
doi:
Substances chimiques
Wnt Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0239083Subventions
Organisme : NICHD NIH HHS
ID : R01 HD073434
Pays : United States
Organisme : NICHD NIH HHS
ID : P01 HD035946
Pays : United States
Organisme : NICHD NIH HHS
ID : R13 HD100191
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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