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Cited by 20Spinal Dysraphism and MalformationsGenomics and Rare DiseasesCongenital gastrointestinal and neural anomalies

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

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Au, K. S., Hebert, L., Hillman, P., Baker, C., Brown, M. R., Kim, D.-K., Soldano, K., Garrett, M. +6 more·2021·Scientific Reports
DOI 10.1038/s41598-021-83058-7PMC PMC7878900
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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.

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  • Two missense variants in ABI1, c.584C > T (p.Thr195Ile) and c.1238A > C (p.Glu413Ala), were found in patients with myelomeningocele and autism spectrum disorder, respectively.

    “Additionally, two missense variants, c.584C > T, p.Thr195Ile, and c.1238A > C, p.Glu413Ala, in ABI1 were found in patients with myelomeningocele (spina bifida)138 and ASD104,114, respectively.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [138]

    Citation 138 is attached to the myelomeningocele finding, not the ASD finding. The Results section reports missense variants in the myelomeningocele cohort, but our copy does not identify ABI1 c.584C > T (p.Thr195Ile) among them; searches for ABI1 and the variant found no confirming passage. Page numbers were unavailable. (LLM, conf=0.70)

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Authors
Au, K. S., Hebert, L., Hillman, P., Baker, C., Brown, M. R., Kim, D.-K., Soldano, K., Garrett, M., Ashley-Koch, A., Lee, S., Gleeson, J., Hixson, J. E., Morrison, A. C., & Northrup, H.
Affiliations
  • The University of Texas Health Science Center at Houston (US)
  • University of Nebraska Medical Center (US)
  • Duke Medical Center (US)
  • University of California San Diego (US)
Corresponding author
Au, K. S.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2021-02-11
Volume
11
Issue
1
Pages
3639-3639
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-021-83058-7
PMC
PMC7878900
OpenAlex
W3128832051
Cited by
20
References
2
Citations by year
2026: 2 · 2025: 9 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 1
FWCI
1.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD073434)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Spinal Dysraphism and Malformations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
Keywords
myelomeningocele, neural tube defects, cilia, Wnt signaling, extracellular matrix, cytoskeleton, cell migration, folate metabolism, glucose metabolism, transcriptional regulation, genetic risk factors
MeSH terms
Cell Movement, Cilia, Cytoskeleton, Extracellular Matrix, Female, Humans, Male, Meningomyelocele, Neural Tube Defects, Risk Factors, Gene Deletion, Genetic Predisposition to Disease, Genetic Association Studies, Wnt Signaling Pathway

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