Mutations in planar cell polarity gene SCRIB are associated with spina bifida
| العنوان: | Mutations in planar cell polarity gene SCRIB are associated with spina bifida |
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| المؤلفون: | Richard H. Finnell, Huiping Zhu, Cody Duhon, Gary M. Shaw, M. Elizabeth Ross, Wei Yang, Yunping Lei |
| المصدر: | PLoS ONE, Vol 8, Iss 7, p e69262 (2013) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | lcsh:Medicine, medicine.disease_cause, Madin Darby Canine Kidney Cells, Mice, 0302 clinical medicine, Missense mutation, lcsh:Science, Spinal Dysraphism, Conserved Sequence, Genetics, 0303 health sciences, Mutation, Multidisciplinary, Intracellular Signaling Peptides and Proteins, Cell Polarity, 3. Good health, Protein Transport, medicine.anatomical_structure, Protein Binding, Subcellular Fractions, Research Article, SCRIB, congenital, hereditary, and neonatal diseases and abnormalities, Molecular Sequence Data, Mutation, Missense, Biology, 03 medical and health sciences, Open Reading Frames, Dogs, Anencephaly, medicine, Craniorachischisis, Animals, Humans, Genetic Predisposition to Disease, Amino Acid Sequence, Gene, Genetic Association Studies, 030304 developmental biology, Spina bifida, Tumor Suppressor Proteins, lcsh:R, Neural tube, Infant, Membrane Proteins, medicine.disease, nervous system diseases, HEK293 Cells, lcsh:Q, 030217 neurology & neurosurgery |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74689a453b93a9ebd5df5631a4bfe929 http://europepmc.org/articles/PMC3724847?pdf=render |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....74689a453b93a9ebd5df5631a4bfe929 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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