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18 results on '"Panchagnula, Shreyas"'

1. Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia

Author

Dong, Weilai, Jin, Sheng Chih, Allocco, August, Zeng, Xue, Sheth, Amar H., Panchagnula, Shreyas, Castonguay, Annie, Lorenzo, Louis-Étienne, Islam, Barira, Brindle, Geneviève, Bachand, Karine, Hu, Jamie, Sularz, Agata, Gaillard, Jonathan, Choi, Jungmin, Dunbar, Ashley, Nelson-Williams, Carol, Kiziltug, Emre, Furey, Charuta Gavankar, Conine, Sierra, Duy, Phan Q., Kundishora, Adam J., Loring, Erin, Li, Boyang, Lu, Qiongshi, Zhou, Geyu, Liu, Wei, Li, Xinyue, Sierant, Michael C., Mane, Shrikant, Castaldi, Christopher, López-Giráldez, Francesc, Knight, James R., Sekula, Raymond F., Jr., Simard, J. Marc, Eskandar, Emad N., Gottschalk, Christopher, Moliterno, Jennifer, Günel, Murat, Gerrard, Jason L., Dib-Hajj, Sulayman, Waxman, Stephen G., Barker, Fred G., II, Alper, Seth L., Chahine, Mohamed, Haider, Shozeb, De Koninck, Yves, Lifton, Richard P., and Kahle, Kristopher T.

Published
2020
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2. Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus

Author

Jin, Sheng Chih, Dong, Weilai, Kundishora, Adam J., Panchagnula, Shreyas, Moreno-De-Luca, Andres, Furey, Charuta G., and Allocco, August A.

Subjects
Hydrocephalus -- Genetic aspects -- Identification and classification -- Diagnosis, Exome sequencing -- Testing -- Patient outcomes -- Methods, Biological sciences, Health
Abstract

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 ~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. The largest whole-exome sequencing study of sporadic congenital hydrocephalus identities mutations associated with disrupted fetal neuro-gliogenesis as the primary pathophysiological event in a significant number of cases., Author(s): Sheng Chih Jin [sup.1] [sup.2] [sup.3] , Weilai Dong [sup.1] [sup.2] , Adam J. Kundishora [sup.4] , Shreyas Panchagnula [sup.4] , Andres Moreno-De-Luca [sup.5] , Charuta G. Furey [sup.4] [...]

Published
2020
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3. Rare pathogenic variants in WNK3 cause X-linked intellectual disability

Author

Küry, Sébastien, primary, Zhang, Jinwei, additional, Besnard, Thomas, additional, Caro-Llopis, Alfonso, additional, Zeng, Xue, additional, Robert, Stephanie M., additional, Josiah, Sunday S., additional, Kiziltug, Emre, additional, Denommé-Pichon, Anne-Sophie, additional, Cogné, Benjamin, additional, Kundishora, Adam J., additional, Hao, Le T., additional, Li, Hong, additional, Stevenson, Roger E., additional, Louie, Raymond J., additional, Deb, Wallid, additional, Torti, Erin, additional, Vignard, Virginie, additional, McWalter, Kirsty, additional, Raymond, F. Lucy, additional, Rajabi, Farrah, additional, Ranza, Emmanuelle, additional, Grozeva, Detelina, additional, Coury, Stephanie A., additional, Blanc, Xavier, additional, Brischoux-Boucher, Elise, additional, Keren, Boris, additional, Õunap, Katrin, additional, Reinson, Karit, additional, Ilves, Pilvi, additional, Wentzensen, Ingrid M., additional, Barr, Eileen E., additional, Guihard, Solveig Heide, additional, Charles, Perrine, additional, Seaby, Eleanor G., additional, Monaghan, Kristin G., additional, Rio, Marlène, additional, van Bever, Yolande, additional, van Slegtenhorst, Marjon, additional, Chung, Wendy K., additional, Wilson, Ashley, additional, Quinquis, Delphine, additional, Bréhéret, Flora, additional, Retterer, Kyle, additional, Lindenbaum, Pierre, additional, Scalais, Emmanuel, additional, Rhodes, Lindsay, additional, Stouffs, Katrien, additional, Pereira, Elaine M., additional, Berger, Sara M., additional, Milla, Sarah S., additional, Jaykumar, Ankita B., additional, Cobb, Melanie H., additional, Panchagnula, Shreyas, additional, Duy, Phan Q., additional, Vincent, Marie, additional, Mercier, Sandra, additional, Gilbert-Dussardier, Brigitte, additional, Le Guillou, Xavier, additional, Audebert-Bellanger, Séverine, additional, Odent, Sylvie, additional, Schmitt, Sébastien, additional, Boisseau, Pierre, additional, Bonneau, Dominique, additional, Toutain, Annick, additional, Colin, Estelle, additional, Pasquier, Laurent, additional, Redon, Richard, additional, Bouman, Arjan, additional, Rosenfeld, Jill. A., additional, Friez, Michael J., additional, Pérez-Peña, Helena, additional, Akhtar Rizvi, Syed Raza, additional, Haider, Shozeb, additional, Antonarakis, Stylianos E., additional, Schwartz, Charles E., additional, Martínez, Francisco, additional, Bézieau, Stéphane, additional, Kahle, Kristopher T., additional, and Isidor, Bertrand, additional

Published
2022
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5. PTEN mutations in autism spectrum disorder and congenital hydrocephalus: developmental pleiotropy and therapeutic targets

Author

DeSpenza, Tyrone, primary, Carlson, Marina, additional, Panchagnula, Shreyas, additional, Robert, Stephanie, additional, Duy, Phan Q., additional, Mermin-Bunnell, Nell, additional, Reeves, Benjamin C., additional, Kundishora, Adam, additional, Elsamadicy, Aladine A., additional, Smith, Hannah, additional, Ocken, Jack, additional, Alper, Seth L., additional, Jin, Sheng Chih, additional, Hoffman, Ellen J., additional, and Kahle, Kristopher T., additional

Published
2021
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6. DIAPH1 Variants in Non–East Asian Patients With Sporadic Moyamoya Disease

Author

Kundishora, Adam J., primary, Peters, Samuel T., additional, Pinard, Amélie, additional, Duran, Daniel, additional, Panchagnula, Shreyas, additional, Barak, Tanyeri, additional, Miyagishima, Danielle F., additional, Dong, Weilai, additional, Smith, Hannah, additional, Ocken, Jack, additional, Dunbar, Ashley, additional, Nelson-Williams, Carol, additional, Haider, Shozeb, additional, Walker, Rebecca L., additional, Li, Boyang, additional, Zhao, Hongyu, additional, Thumkeo, Dean, additional, Marlier, Arnaud, additional, Duy, Phan Q., additional, Diab, Nicholas S., additional, Reeves, Benjamin C., additional, Robert, Stephanie M., additional, Sujijantarat, Nanthiya, additional, Stratman, Amber N., additional, Chen, Yi-Hsien, additional, Zhao, Shujuan, additional, Roszko, Isabelle, additional, Lu, Qiongshi, additional, Zhang, Bo, additional, Mane, Shrikant, additional, Castaldi, Christopher, additional, López-Giráldez, Francesc, additional, Knight, James R., additional, Bamshad, Michael J., additional, Nickerson, Deborah A., additional, Geschwind, Daniel H., additional, Chen, Shih-Shan Lang, additional, Storm, Phillip B., additional, Diluna, Michael L., additional, Matouk, Charles C., additional, Orbach, Darren B., additional, Alper, Seth L., additional, Smith, Edward R., additional, Lifton, Richard P., additional, Gunel, Murat, additional, Milewicz, Dianna M., additional, Jin, Sheng Chih, additional, and Kahle, Kristopher T., additional

Published
2021
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7. Clinical Outcomes between Stand-Alone Zero-Profile Spacers and Cervical Plate with Cage Fixation for Anterior Cervical Discectomy and Fusion: A Retrospective Analysis of 166 Patients

Author

Sommaruga, Samuel, primary, Camara-Quintana, Joaquin, additional, Patel, Kishan, additional, Nouri, Aria, additional, Tessitore, Enrico, additional, Molliqaj, Granit, additional, Panchagnula, Shreyas, additional, Robinson, Michael, additional, Virojanapa, Justin, additional, Sun, Xin, additional, Melnikov, Fjodor, additional, Kolb, Luis, additional, Schaller, Karl, additional, Abbed, Khalid, additional, and Cheng, Joseph, additional

Published
2021
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9. Integrative Genomics Implicates Genetic Disruption of Prenatal Neurogenesis in Congenital Hydrocephalus

Author

Panchagnula, Shreyas, primary, Jin, Sheng C, additional, Dong, Weilai, additional, Kundishora, Adam, additional, Moreno-De-Luca, Andres, additional, Furey, Charuta G, additional, Allocco, August A, additional, Walker, Rebecca, additional, Nelson-Williams, Carol, additional, Smith, Hannah, additional, Dunbar, Ashley, additional, Conine, Sierra B, additional, Lu, Qiongshi, additional, Zen, Xue, additional, Sierant, Michael, additional, Knight, James, additional, Sullivan, William, additional, Phan, Duy, additional, DeSpenza, Tyrone, additional, Reeves, Benjamin, additional, Karimy, Jason K, additional, Marlier, Arnaud, additional, Castaldi, Christopher, additional, Tikhonova, Irina, additional, Li, Boyang, additional, Peña;, Helena, additional, Broach, James, additional, Kabachelor, Edith M, additional, Ssenyonga, Peter, additional, Hehnly, Christine, additional, Ge, Li, additional, Keren, Boris, additional, Timberlake, Andrew T, additional, Goto, June, additional, Mangano, Francesco T, additional, Johnston, James M, additional, Butler, William, additional, Warf, Benjamin C, additional, Smith, Edward R, additional, Schiff, Steven J, additional, Limbrick, David D, additional, Heuer, Gregory G, additional, Jackson, Eric M, additional, Iskandar, Bermans J, additional, Mane, Shrikant, additional, Haider, Shozeb, additional, Guclu, Bulent, additional, Bayri, Yasar, additional, Sahin, Yener, additional, Duncan, Charles C, additional, Apuzzo, Michael L.J, additional, DiLuna, Michael L, additional, Hoffman, Ellen, additional, Sestan, Nenad, additional, Ment, Laura, additional, Alper, Seth, additional, Bilguvar, Kaya, additional, Geschwind, Daniel, additional, Günel, Murat, additional, Lifton, Richard P, additional, and Kahle, Kristopher T, additional

Published
2020
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10. Exome Sequencing Defines the Molecular Pathogenesis of Vein of Galen Malformation

Author

Kundishora, Adam, primary, Zeng, Xue, additional, Duran, Daniel, additional, Allocco, August A, additional, Choi, Jungmin, additional, Jin, Sheng Chih, additional, Conine, Sierra B, additional, Nelson-Williams, Carol, additional, Gaillard, Jonathan, additional, Furey, Charuta G, additional, Timberlake, Andrew T, additional, Mansuri, Mohammad, additional, Sorscher, Michelle, additional, Klein, Jennifer, additional, Lu, Qiongshi, additional, Montejo, Julio D, additional, Vera, Alberto, additional, Karimy, Jason K, additional, Panchagnula, Shreyas, additional, Youngblood, Mark, additional, DiLuna, Michael L, additional, Matouk, Charles C, additional, Mane, Shrikant, additional, Alper, Seth, additional, Ducruet, Andrew F, additional, Zabramski, Joseph M, additional, Aagaard-Kienitz, Beverly, additional, Rodesch, Georges, additional, Smith, Edward R, additional, Orbach, Darren, additional, Berenstein, Alejandro, additional, Bilguvar, Kaya, additional, Gunel, Murat, additional, Lifton, Richard P, additional, and Kahle, Kristopher T, additional

Published
2019
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12. 116 Exome Sequencing Uncovers Molecular Determinants of Trigeminal Neuralgia

Author

Choi, Jungmin, primary, Zeng, Xue, additional, Jin, Sheng Chih, additional, Gaillard, Jonathan, additional, Duran, Daniel, additional, Nelson-Williams, Carol, additional, Panchagnula, Shreyas, additional, Dib-Hajj, Sulayman, additional, Barker, Frederick G, additional, Sekula, Raymond F, additional, Waxman, Stephen, additional, Gunel, Murat, additional, Lifton, Richard P, additional, and T., Kristopher, additional

Published
2018
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13. 125 De Novo Mutations in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus

Author

Furey, Charuta Gavankar, primary, Jin, Sheng Chih, additional, Timberlake, Andrew T, additional, Choi, Jungmin, additional, Zeng, Xue, additional, Nelson-Williams, Carol, additional, Mansuri, Mohammad, additional, Lu, Qiongshi, additional, Duran, Daniel, additional, Panchagnula, Shreyas, additional, Alloco, August, additional, Karimy, Jason K, additional, Gaillard, Jonathan, additional, Khanna, Arjun, additional, Butler, William, additional, Smith, Edward R, additional, Warf, Benjamin C, additional, Limbrick, David D, additional, Storm, Phillip B, additional, Heuer, Gregory G, additional, Iskandar, Bermans, additional, Johnston, James M, additional, Alper, Seth, additional, Guclu, Bulent, additional, Bayri, Yasar, additional, Sahin, Yener, additional, Duncan, Charles C, additional, DiLuna, Michael L, additional, Gunel, Murat, additional, Lifton, Richard P, additional, and Kahle, Kristopher T, additional

Published
2018
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14. De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus

Author

Furey, Charuta Gavankar, primary, Choi, Jungmin, additional, Jin, Sheng Chih, additional, Zeng, Xue, additional, Timberlake, Andrew T., additional, Nelson-Williams, Carol, additional, Mansuri, M. Shahid, additional, Lu, Qiongshi, additional, Duran, Daniel, additional, Panchagnula, Shreyas, additional, Allocco, August, additional, Karimy, Jason K., additional, Khanna, Arjun, additional, Gaillard, Jonathan R., additional, DeSpenza, Tyrone, additional, Antwi, Prince, additional, Loring, Erin, additional, Butler, William E., additional, Smith, Edward R., additional, Warf, Benjamin C., additional, Strahle, Jennifer M., additional, Limbrick, David D., additional, Storm, Phillip B., additional, Heuer, Gregory, additional, Jackson, Eric M., additional, Iskandar, Bermans J., additional, Johnston, James M., additional, Tikhonova, Irina, additional, Castaldi, Christopher, additional, López-Giráldez, Francesc, additional, Bjornson, Robert D., additional, Knight, James R., additional, Bilguvar, Kaya, additional, Mane, Shrikant, additional, Alper, Seth L., additional, Haider, Shozeb, additional, Guclu, Bulent, additional, Bayri, Yasar, additional, Sahin, Yener, additional, Apuzzo, Michael L.J., additional, Duncan, Charles C., additional, DiLuna, Michael L., additional, Günel, Murat, additional, Lifton, Richard P., additional, and Kahle, Kristopher T., additional

Published
2018
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16. Rare pathogenic variants in WNK3cause X-linked intellectual disability

Author

Küry, Sébastien, Zhang, Jinwei, Besnard, Thomas, Caro-Llopis, Alfonso, Zeng, Xue, Robert, Stephanie M., Josiah, Sunday S., Kiziltug, Emre, Denommé-Pichon, Anne-Sophie, Cogné, Benjamin, Kundishora, Adam J., Hao, Le T., Li, Hong, Stevenson, Roger E., Louie, Raymond J., Deb, Wallid, Torti, Erin, Vignard, Virginie, McWalter, Kirsty, Raymond, F. Lucy, Rajabi, Farrah, Ranza, Emmanuelle, Grozeva, Detelina, Coury, Stephanie A., Blanc, Xavier, Brischoux-Boucher, Elise, Keren, Boris, Õunap, Katrin, Reinson, Karit, Ilves, Pilvi, Wentzensen, Ingrid M., Barr, Eileen E., Guihard, Solveig Heide, Charles, Perrine, Seaby, Eleanor G., Monaghan, Kristin G., Rio, Marlène, van Bever, Yolande, van Slegtenhorst, Marjon, Chung, Wendy K., Wilson, Ashley, Quinquis, Delphine, Bréhéret, Flora, Retterer, Kyle, Lindenbaum, Pierre, Scalais, Emmanuel, Rhodes, Lindsay, Stouffs, Katrien, Pereira, Elaine M., Berger, Sara M., Milla, Sarah S., Jaykumar, Ankita B., Cobb, Melanie H., Panchagnula, Shreyas, Duy, Phan Q., Vincent, Marie, Mercier, Sandra, Gilbert-Dussardier, Brigitte, Le Guillou, Xavier, Audebert-Bellanger, Séverine, Odent, Sylvie, Schmitt, Sébastien, Boisseau, Pierre, Bonneau, Dominique, Toutain, Annick, Colin, Estelle, Pasquier, Laurent, Redon, Richard, Bouman, Arjan, Rosenfeld, Jill. A., Friez, Michael J., Pérez-Peña, Helena, Akhtar Rizvi, Syed Raza, Haider, Shozeb, Antonarakis, Stylianos E., Schwartz, Charles E., Martínez, Francisco, Bézieau, Stéphane, Kahle, Kristopher T., and Isidor, Bertrand

Abstract

WNK3 kinase (PRKWNK3) has been implicated in the development and function of the brain via its regulation of the cation-chloride cotransporters, but the role of WNK3 in human development is unknown.

Published
2022
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17. Validating the Transformation of PROMIS-GH to EQ-5D in Adult Spine Patients.

Author

Panchagnula, Shreyas, Sun, Xin, Montejo, Julio D., Nouri, Aria, Kolb, Luis, Virojanapa, Justin, Camara-Quintana, Joaquin Q., Sommaruga, Samuel, Patel, Kishan, Lakomkin, Nikita, Abbed, Khalid, and Cheng, Joseph S.

Subjects
*SPINE, *AGE groups, *INFORMATION measurement, *INFORMATION storage & retrieval systems, *ECONOMIC surveys
Abstract

Spinal disorders and associated interventions are costly in the United States, putting them in the limelight of economic analyses. The Patient-Reported Outcomes Measurement Information System Global Health Survey (PROMIS-GHS) requires mapping to other surveys for economic investigation. Previous studies have proposed transformations of PROMIS-GHS to EuroQol 5-Dimension (EQ-5D) health index scores. These models require validation in adult spine patients. In our study, PROMIS-GHS and EQ-5D were randomly administered to 121 adult spine patients. The actual health index scores were calculated from the EQ-5D instrument and estimated scores were calculated from the PROMIS-GHS responses with six models. Goodness-of-fit for each model was determined using the coefficient of determination (R2), mean squared error (MSE), and mean absolute error (MAE). Among the models, the model treating the eight PROMIS-GHS items as categorical variables (CATReg) was the optimal model with the highest R2 (0.59) and lowest MSE (0.02) and MAE (0.11) in our spine sample population. Subgroup analysis showed good predictions of the mean EQ-5D by gender, age groups, education levels, etc. The transformation from PROMIS-GHS to EQ-5D had a high accuracy of mean estimate on a group level, but not at the individual level. [ABSTRACT FROM AUTHOR]

Published
2019
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18. Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus

Author

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, 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., and Kahle, Kristopher T.

Subjects
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
Abstract

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.

Published
2020

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