Mutations in Planar Cell Polarity Gene SCRIB Are Associated with Spina Bifida

Details

• Alternative Title:
  PLoS One
• Personal Author:
  Lei, Yunping ; Zhu, Huiping ; Duhon, Cody ; Yang, Wei ; Ross, M. Elizabeth ; Shaw, Gary M. ; Finnell, Richard H.
• Description:
  Neural tube defects (NTDs) (OMIM #182940) including anencephaly, spina bifida and craniorachischisis, are severe congenital malformations that affect 0.5-1 in 1,000 live births in the United States, with varying prevalence around the world. Mutations in planar cell polarity (PCP) genes are believed to cause a variety of NTDs in both mice and humans. SCRIB is a PCP-associated gene. Mice that are homozygous for the Scrib p.I285K and circletail (Crc) mutations, present with the most severe form of NTDs, namely craniorachischisis. A recent study reported that mutations in SCRIB were associated with craniorachischisis in humans, but whether SCRIB mutations contribute to increased spina bifida risk is still unknown. We sequenced the SCRIB gene in 192 infants with spina bifida and 190 healthy controls. Among the spina bifida patients, we identified five novel missense mutations that were predicted-to-be-deleterious by the PolyPhen software. Of these five mutations, three of them (p.P1043L, p.P1332L, p.L1520R) significantly affected the subcellular localization of SCRIB. In addition, we demonstrated that the craniorachischisis mouse line-90 mutation I285K, also affected SCRIB subcellular localization. In contrast, only one novel missense mutation (p.A1257T) was detected in control samples, and it was predicted to be benign. This study demonstrated that rare deleterious mutations of SCRIB may contribute to the multifactorial risk for human spina bifida.
• Subjects:
  Amino Acid Sequence Animals Cell Polarity Conserved Sequence Dogs Genetic Association Studies Genetic Predisposition To Disease HEK293 Cells Humans Infant Intracellular Signaling Peptides And Proteins Madin Darby Canine Kidney Cells Membrane Proteins Mice Molecular Sequence Data Mutation Mutation, Missense Open Reading Frames Protein Binding Protein Transport Spinal Dysraphism Subcellular Fractions Tumor Suppressor Proteins

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• Source:
  PLoS One. 2013; 8(7).
• Pubmed ID:
  23922697
• Pubmed Central ID:
  PMC3724847
• Document Type:
  Journal Article
• Funding:
  HD067244/HD/NICHD NIH HHS/United States ; NS076465/NS/NINDS NIH HHS/United States ; P01 HD067244/HD/NICHD NIH HHS/United States ; R01 ES021006/ES/NIEHS NIH HHS/United States ; R01-NS050249/NS/NINDS NIH HHS/United States ; U01/DD000491/DD/NCBDD CDC HHS/United States
• Volume:
  8
• Issue:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:d41cd7a1614c1aa1e61950ed74836a43b06101950b98a69a91c01c410921aee9
• Download URL:
  https://stacks.cdc.gov/view/cdc/22582/cdc_22582_DS1.pdf
• File Type:
  [PDF - 1.11 MB ]