Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus
| العنوان: | Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus |
|---|---|
| المؤلفون: | William J. Sullivan, Bermans J. Iskandar, Yasar Bayri, James R. Knight, James M. Johnston, Michael L.J. Apuzzo, Kristopher T. Kahle, Boyang Li, Andrew T. Timberlake, Sheng Chih Jin, Steven J. Schiff, Shreyas Panchagnula, Rebecca L. Walker, Shozeb Haider, Li Ge, Daniel H. Geschwind, Hannah Smith, Richard P. Lifton, Seth L. Alper, Carol Nelson-Williams, Boris Keren, Christine Hehnly, Arnaud Marlier, Bulent Guclu, Laura R. Ment, Ellen J. Hoffman, Francesco T. Mangano, Xue Zeng, Edith Mbabazi Kabachelor, Kaya Bilguvar, August A Allocco, Ashley Dunbar, James R. Broach, Benjamin C. Warf, William E. Butler, Helena Perez Pena, Sierra B Conine, David D. Limbrick, Qiongshi Lu, Edward R. Smith, Jason K. Karimy, Christopher Castaldi, Eric M. Jackson, Yener Sahin, Murat Gunel, Adam J. Kundishora, Charles C. Duncan, Michael L. DiLuna, Shrikant Mane, Michael C. Sierant, Gregory G. Heuer, June Goto, Charuta G. Furey, Andres Moreno-De-Luca, Peter Ssenyonga, Weilai Dong, Nenad Sestan, Phan Q. Duy, Benjamin C. Reeves, Tyrone DeSpenza, Irina Tikhonova |
| المساهمون: | Jin, Sheng Chih, Dong, Weilai, Kundishora, Adam J., Panchagnula, Shreyas, Moreno-De-Luca, Andres, Furey, Charuta G., Allocco, August A., Walker, Rebecca L., Nelson-Williams, Carol, Smith, Hannah, Dunbar, Ashley, Conine, Sierra, Lu, Qiongshi, Zeng, Xue, Sierant, Michael C., Knight, James R., Sullivan, William, Duy, Phan Q., DeSpenza, Tyrone, Reeves, Benjamin C., Karimy, Jason K., Marlier, Arnaud, Castaldi, Christopher, Tikhonova, Irina R., Li, Boyang, Pena, Helena Perez, Broach, James R., Kabachelor, Edith M., Ssenyonga, Peter, Hehnly, Christine, Ge, Li, Keren, Boris, Timberlake, Andrew T., Goto, June, Mangano, Francesco T., Johnston, James M., Butler, William E., Warf, Benjamin C., Smith, Edward R., Schiff, Steven J., Limbrick, David D., Jr., Heuer, Gregory, Jackson, Eric M., Iskandar, Bermans J., Mane, Shrikant, Haider, Shozeb, Guclu, Bulent, Bayri, Yasar, Sahin, Yener, Duncan, Charles C., Apuzzo, Michael L. J., DiLuna, Michael L., Hoffman, Ellen J., Sestan, Nenad, Ment, Laura R., Alper, Seth L., Bilguvar, Kaya, Geschwind, Daniel H., Gunel, Murat, Lifton, Richard P., Kahle, Kristopher T. |
| المصدر: | Nat Med |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | EXPRESSION, 0301 basic medicine, Male, PTEN, Cell type, Neurogenesis, Ubiquitin-Protein Ligases, CHILDREN, Disease, VENTRICULAR ZONE DISRUPTION, Bioinformatics, General Biochemistry, Genetics and Molecular Biology, Article, COWDEN-SYNDROME, Cerebral Ventricles, PATHWAY, Tripartite Motif Proteins, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, RARE, Neural Stem Cells, Pregnancy, Exome Sequencing, Medicine, Humans, Genetic Predisposition to Disease, Exome, AUTISM, Exome sequencing, Gliogenesis, SPECTRUM, Fetus, business.industry, Brain, General Medicine, medicine.disease, Neural stem cell, DE-NOVO MUTATION, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Female, business, Neuroglia, Ventriculomegaly, Transcription Factors, Hydrocephalus |
| الوصف: | Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to similar to 22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa5ffd2d8f3b89a9eace21cef26b4737Test https://europepmc.org/articles/PMC7871900Test/ |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fa5ffd2d8f3b89a9eace21cef26b4737 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |