Skip to main content Accessibility help
×
Hostname: page-component-78c5997874-j824f Total loading time: 0 Render date: 2024-11-08T22:26:47.384Z Has data issue: false hasContentIssue false

How We Got to Where We're Going

Published online by Cambridge University Press:  31 August 2021

Annapurna H. Poduri
Affiliation:
Boston Children’s Hospital and Harvard Medical School
Alfred L. George Jr
Affiliation:
Northwestern University Feinberg School of Medicine
Erin L. Heinzen
Affiliation:
University of North Carolina, Chapel Hill
Daniel Lowenstein
Affiliation:
University of California, San Francisco
Sara James
Affiliation:
Journalist and author

Summary

This Element serves as a welcome to the Cambridge Elements Genetics in Epilepsy series. The series editors look forward to sharing with you the story of epilepsy genetics through a series of Elements. They will bring together many voices, by text as well as video, to illustrate the history of epilepsy genetics, the many on-going efforts in the field, and how they hope to address the still unanswered questions that command the attention of all of us and our colleagues across the globe.
Get access
Type
Element
Information
Online ISBN: 9781009000420
Publisher: Cambridge University Press
Print publication: 30 September 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Temkin, O., The Falling Sickness (Baltimore MD: The Johns Hopkins Press; 1945).Google Scholar
Reynolds, J. R., Epilepsy: Its Symptoms, Treatment, and Relation to Other Chronic Convulsive Diseases (John Churchill; 1861).Google Scholar
Leuret, F., Recherches sur l’epilepsie, Archives Generales de Medecine, 4th series, 2 (1843), 3250.Google Scholar
Lennox, W. G., Lennox, M. A., The Genetics of Epilepsy. Epilepsy and Related Disorders, vol. 1 (Boston MA: Little, Brown; 1960), pp. 532–74.Google Scholar
Annegers, J. F., Hauser, W. A., Elveback, L. R., Anderson, V. E., Kurland, L. I., Congenital malformations and seizure disorders in the offspring of parents with epilepsy, Int J Epidemiol, 7 (1978), 241–7. DOI: https://doi.org/10.1093/ije/7.3.241.CrossRefGoogle ScholarPubMed
Annegers, J. F., Hauser, W. A., Anderson, V. E., Kurland, L. T., The risks of seizure disorders among relatives of patients with childhood onset epilepsy, Neurology, 32 (1982), 174–9. DOI: https://doi.org/10.1212/wnl.32.2.174.Google Scholar
Leppert, M., Anderson, V. E., Quattlebaum, T., Stauffer, D., O’Connell, P., Nakamura, Y., et al., Benign familial neonatal convulsions linked to genetic markers on chromosome 20, Nature, 337 (1989), 647–8. DOI: https://doi.org/10.1038/337647a0.Google Scholar
Biervert, C., Schroeder, B. C., Kubisch, C., Berkovic, S. F., Propping, P., Jentsch, T. J., et al., A potassium channel mutation in neonatal human epilepsy, Science, 279 (1998), 403–6. DOI: https://doi.org/10.1126/science.279.5349.403.CrossRefGoogle ScholarPubMed
Steinlein, O. K., Mulley, J. C., Propping, P., Wallace, R. H., Phillips, H. A., Sutherland, G. R., et al., A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy, Nat Genet, 11 (1995), 201–3. DOI: https://doi.org/10.1038/ng1095-201.Google Scholar
Consortium, EPICURE, Consortium, EMINet, Steffens, M., Leu, C., Ruppert, A. K., Zara, F., et al., Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32, Hum Mol Genet, 21 (2012), 5359–72. DOI: https://doi.org/10.1093/hmg/dds373.Google Scholar
International Human Genome Sequencing Consortium, Finishing the euchromatic sequence of the human genome, Nature, 431 (2004), 931–45. DOI: https://doi.org/10.1038/nature03001.Google Scholar
International HapMap Consortium, The International HapMap Project, Nature, 426 (2003), 789–96. DOI: https://doi.org/10.1038/nature02168.Google Scholar
1000 Genomes Project Consortium, Auton, A., Brooks, L. D., Durbin, R. M., Garrison, E. P., Kang, H. M., et al., A global reference for human genetic variation, Nature, 526 (2015), 6874. DOI: https://doi.org/10.1038/nature15393.Google Scholar
Fryer, A. E., Chalmers, A., Connor, J. M., Fraser, I., Povey, S., Yates, A. D., et al., Evidence that the gene for tuberous sclerosis is on chromosome 9, Lancet, 1 (1987), 659–61. DOI: https://doi.org/10.1016/s0140-6736(87)90416-8.Google Scholar
Kandt, R. S., Haines, J. L., Smith, M., Northrup, H., Gardner, R. J., Short, M. P., et al., Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease, Nat Genet, 2 (1992), 3741. DOI: https://10.1038/ng0992-37.CrossRefGoogle ScholarPubMed
Chromosome, European 16 Tuberous Sclerosis Consortium, Identification and characterization of the tuberous sclerosis gene on chromosome 16, Cell, 75 (1993), 1305–15. DOI: https://doi.org/10.1016/0092-8674(93)90618-z.Google Scholar
van Slegtenhorst, M., de Hoogt, R., Hermans, C., Nellist, M., Janssen, B., Verhoef, S., et al., Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34, Science, 277 (1997), 805–8. DOI: https://doi.org/10.1126/science.277.5327.805.Google Scholar
Consortium, EPICURE, Leu, C., de Kovel, C. G., Zara, F., Striano, P., Pezzella, M., et al., Genome-wide linkage meta-analysis identifies susceptibility loci at 2q34 and 13q31.3 for genetic generalized epilepsies, Epilepsia, 53 (2012), 308–18. DOI: https://doi.org/10.1111/j.1528-1167.2011.03379.x.Google Scholar
International League Against Epilepsy Consortium on Complex Epilepsies, Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies, Lancet Neurol, 13 (2014), 893903. DOI: https://doi.org/10.1016/S1474-4422(14)70171-1.CrossRefGoogle Scholar
International League Against Epilepsy Consortium on Complex Epilepsies, Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies, Nat Commun, 9 (2018), 5269. DOI: https://doi.org/10.1038/s41467-018-07524-z.Google Scholar
Carvill, G. L., McMahon, J. M., Schneider, A., Zemel, M., Myers, C. T., Saykally, J., et al., Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures, Am J Hum Genet, 96 (2015), 808–15. DOI: https://doi.org/10.1016/j.ajhg.2015.02.016.Google Scholar
Euro-EPINOMICS-RES Consortium, Epilepsy Phenome/Genome Project, Epi4K Consortium, De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies, Am J Hum Genet, 95 (2014), 360–70. DOI: https://doi.org/10.1016/j.ajhg.2014.08.013.Google Scholar
Nava, C., Dalle, C., Rastetter, A., Striano, P., de Kovel, C. G., Nabbout, R., et al., De novo mutations in HCN1 cause early infantile epileptic encephalopathy, Nat Genet, 46 (2014), 640–5. DOI: https://doi.org/10.1038/ng.2952.CrossRefGoogle ScholarPubMed
Schubert, J., Siekierska, A., Langlois, M., May, P., Huneau, C., Becker, F., et al., Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes, Nat Genet, 46 (2014), 1327–32. DOI: https://doi.org/10.1038/ng.3130.CrossRefGoogle ScholarPubMed
Suls, A., Jaehn, J. A., Kecskes, A., Weber, Y., Weckhuysen, S., Craiu, D. C., et al., De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome, Am J Hum Genet, 93 (2013), 967–75. DOI: https://doi.org/10.1016/j.ajhg.2013.09.017.Google Scholar
Syrbe, S., Hedrich, U. B. S., Riesch, E., Djemie, T., Muller, S., Moller, R. S., et al., De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy, Nat Genet, 47 (2015), 393–9. DOI: https://doi.org/10.1038/ng.3239.Google Scholar
Tang, S., Addis, L., Smith, A., Topp, S. D., Pendziwiat, M., Mei, D., et al., Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures, Epilepsia, 61 (2020), 9951007. DOI: https://doi.org/10.1111/epi.16508.Google Scholar
Larsen, J., Carvill, G. L., Gardella, E., Kluger, G., Schmiedel, G., Barisic, N., et al., The phenotypic spectrum of SCN8A encephalopathy, Neurology, 84 (2015), 480–9. DOI: https://doi.org/10.1212/WNL.0000000000001211.Google Scholar
Lal, D., Steinbrucker, S., Schubert, J., Sander, T., Becker, F., Weber, Y., et al., Investigation of GRIN2A in common epilepsy phenotypes, Epilepsy Res, 115 (2015), 95–9. DOI: https://doi.org/10.1016/j.eplepsyres.2015.05.010.CrossRefGoogle ScholarPubMed
Heyne, H. O., Singh, T., Stamberger, H., Abou Jamra, R., Caglayan, H., Craiu, D., et al., De novo variants in neurodevelopmental disorders with epilepsy, Nat Genet, 50 (2018), 1048–53. DOI: https://doi.org/10.1038/s41588-018-0143-7.Google Scholar
Marini, C., Porro, A., Rastetter, A., Dalle, C., Rivolta, I., Bauer, D., et al., HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond, Brain, 141 (2018), 3160–78. DOI: https://doi.org/10.1093/brain/awy263.Google Scholar
Mignot, C., von Stulpnagel, C., Nava, C., Ville, D., Sanlaville, D., Lesca, G., et al., Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy, J Med Genet, 53 (2016), 511–22. DOI: https://doi.org/10.1136/jmedgenet-2015-103451.Google Scholar
Collaborative, EPGP, Abou-Khalil, B., Alldredge, B., Bautista, J., Berkovic, S., Bluvstein, J., et al., The epilepsy phenome/genome project, Clin Trials, 10 (2013), 568–86. DOI: https://doi.org/10.1177/1740774513484392.Google Scholar
McGovern, K., Karn, C. F., Fox, K., Investigators, E., surpassing the target: how a recruitment campaign transformed the participant accrual trajectory in the Epilepsy Phenome/Genome Project, Clin Transl Sci, 8 (2015), 518–25. DOI: https://doi.org/10.1111/cts.12307.Google Scholar
Epi4K Consortium, Epi4K: gene discovery in 4,000 genomes, Epilepsia, 53 (2012), 1457–67. DOI: https://doi.org/10.1111/j.1528-1167.2012.03511.x.Google Scholar
Epi4K Consortium, Epilepsy Phenome/Genome Project, Allen, A. S., Berkovic, S. F., Cossette, P., Delanty, N., et al., De novo mutations in epileptic encephalopathies, Nature, 501 (2013), 217–21. DOI: https://doi.org/10.1038/nature12439.Google Scholar
von Spiczak, S., Helbig, K. L., Shinde, D. N., Huether, R., Pendziwiat, M., Lourenco, C., et al., DNM1 encephalopathy: A new disease of vesicle fission, Neurology, 89 (2017), 385–94. DOI: https://doi.org/10.1212/WNL.0000000000004152.Google Scholar
Epi4K Consortium, De novo mutations in SLC1A2 and CACNA1A are important causes of epileptic encephalopathies, Am J Hum Genet, 99 (2016), 287–98. DOI: https://doi.org/10.1016/j.ajhg.2016.06.003.Google Scholar
Epi4K Consortium, Epilepsy Phenome/Genome Project, Ultra-rare genetic variation in common epilepsies: a case-control sequencing study, Lancet Neurol, 16 (2017), 135–43. DOI: https://doi.org/10.1016/S1474-4422(16)30359-3.Google Scholar
May, P., Girard, S., Harrer, M., Bobbili, D. R., Schubert, J., Wolking, S., et al., Rare coding variants in genes encoding GABAA receptors in genetic generalised epilepsies: an exome-based case-control study, Lancet Neurol, 17 (2018), 699708. DOI: https://doi.org/10.1016/S1474-4422(18)30215-1.CrossRefGoogle ScholarPubMed
Initiative, Epilepsy Genetics , De novo variants in the alternative exon 5 of SCN8A cause epileptic encephalopathy, Genet Med, 20 (2018), 275–81. DOI: https://doi.org/10.1038/gim.2017.100.Google Scholar
Initiative, Epilepsy Genetics, The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield, Epilepsia, 60 (2019), 797806. DOI: https://doi.org/10.1111/epi.14698.Google Scholar
Wolking, S., Moreau, C., Nies, A. T., Schaeffeler, E., McCormack, M., Auce, P., et al., Testing association of rare genetic variants with resistance to three common antiseizure medications, Epilepsia, 61 (2020), 657–66. DOI: https://doi.org/10.1111/epi.16467.Google Scholar
Wolking, S., Schulz, H., Nies, A. T., McCormack, M., Schaeffeler, E., Auce, P., et al., Pharmacoresponse in genetic generalized epilepsy: a genome-wide association study, Pharmacogenomics, 21 (2020), 325–35. DOI: https://doi.org/10.2217/pgs-2019-0179.Google Scholar
Leu, C., Stevelink, R., Smith, A. W., Goleva, S. B., Kanai, M., Ferguson, L., et al., Polygenic burden in focal and generalized epilepsies, Brain, 142 (2019), 3473–81. DOI: https://doi.org/10.1093/brain/awz292.Google Scholar
Helbig, I., Riggs, E. R., Barry, C. A., Klein, K. M., Dyment, D., Thaxton, C., et al., The ClinGen Epilepsy Gene Curation Expert Panel – Bridging the divide between clinical domain knowledge and formal gene curation criteria, Hum Mutat, 39 (2018), 1476–84. DOI: https://doi.org/10.1002/humu.23632.Google Scholar
Vlaskamp, D. R. M., Shaw, B. J., Burgess, R., Mei, D., Montomoli, M., Xie, H., et al., SYNGAP1 encephalopathy: A distinctive generalized developmental and epileptic encephalopathy, Neurology, 92 (2019), e96-e107. DOI: https://doi.org/10.1212/WNL.0000000000006729.Google Scholar
Berg, A. T., Mahida, S., Poduri, A., KCNQ2-DEE: developmental or epileptic encephalopathy?, Ann Clin Transl Neurol, 8 (2021), 666–76. DOI: https://doi.org/10.1002/acn3.51316.Google Scholar
Berg, A. T., Palac, H., Wilkening, G., Zelko, F., Schust Meyer, L., SCN2A-Developmental and Epileptic Encephalopathies: Challenges to trial-readiness for non-seizure outcomes, Epilepsia, 62 (2021), 258–68. DOI: https://doi.org/10.1111/epi.16750.Google Scholar
Jimenez-Gomez, A., Niu, S., Andujar-Perez, F., McQuade, E. A., Balasa, A., Huss, D., et al., Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression, J Neurodev Disord, 11 (2019), 18. DOI: https://doi.org/10.1186/s11689-019-9276-y.Google Scholar
Lee, J. H., Huynh, M., Silhavy, J. L., Kim, S., Dixon-Salazar, T., Heiberg, A., et al., De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly, Nat Genet, 44 (2012), 941–5. DOI: https://doi.org/10.1038/ng.2329.Google Scholar
Poduri, A., Evrony, G. D., Cai, X., Elhosary, P. C., Beroukhim, R., Lehtinen, M. K., et al., Somatic activation of AKT3 causes hemispheric developmental brain malformations, Neuron, 74 (2012), 41–8. DOI: https://doi.org/10.1016/j.neuron.2012.03.010.Google Scholar
Winawer, M. R., Griffin, N. G., Samanamud, J., Baugh, E. H., Rathakrishnan, D., Ramalingam, S., et al., Somatic SLC35A2 variants in the brain are associated with intractable neocortical epilepsy, Ann Neurol, 83 (2018), 1133–46. DOI: https://doi.org/10.1002/ana.25243.Google Scholar
Loomis, E. W., Eid, J. S., Peluso, P., Yin, J., Hickey, L., Rank, D., et al., Sequencing the unsequenceable: expanded CGG-repeat alleles of the fragile X gene, Genome Res, 23 (2013), 121–8. DOI: https://doi.org/10.1101/gr.141705.112.Google Scholar
Merker, J. D., Wenger, A. M., Sneddon, T., Grove, M., Zappala, Z., Fresard, L., et al., Long-read genome sequencing identifies causal structural variation in a Mendelian disease, Genet Med, 20 (2018), 159–63. DOI: https://doi.org/10.1038/gim.2017.86.Google Scholar
Sanchis-Juan, A., Stephens, J., French, C. E., Gleadall, N., Megy, K., Penkett, C., et al., Complex structural variants in Mendelian disorders: identification and breakpoint resolution using short- and long-read genome sequencing, Genome Med, 10 (2018), 95. DOI: https://doi.org/10.1186/s13073-018-0606-6.Google Scholar
Sone, J., Mitsuhashi, S., Fujita, A., Mizuguchi, T., Hamanaka, K., Mori, K., et al., Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease, Nat Genet, 51 (2019), 1215–21. DOI: https://doi.org/10.1038/s41588-019-0459-y.Google Scholar
Fan, H., Chu, J. Y., A brief review of short tandem repeat mutation, Genomics Proteomics Bioinformatics, 5 (2007), 714. DOI: https://doi.org/10.1016/S1672-0229(07)60009-6.Google Scholar
Cen, Z., Jiang, Z., Chen, Y., Zheng, X., Xie, F., Yang, X., et al., Intronic pentanucleotide TTTCA repeat insertion in the SAMD12 gene causes familial cortical myoclonic tremor with epilepsy type 1, Brain, 141 (2018), 2280–8. DOI: https://doi.org/10.1093/brain/awy160.Google Scholar
Corbett, M. A., Kroes, T., Veneziano, L., Bennett, M. F., Florian, R., Schneider, A. L., et al., Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2, Nat Commun, 10 (2019), 4920. DOI: https://doi.org/10.1038/s41467-019-12671-y.Google Scholar
Florian, R. T., Kraft, F., Leitao, E., Kaya, S., Klebe, S., Magnin, E., et al., Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3, Nat Commun, 10 (2019), 4919. DOI: https://doi.org/10.1038/s41467-019-12763-9.Google Scholar
Ishiura, H., Doi, K., Mitsui, J., Yoshimura, J., Matsukawa, M. K., Fujiyama, A., et al., Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy, Nat Genet, 50 (2018), 581–90. DOI: https://doi.org/10.1038/s41588-018-0067-2.Google Scholar
Mizuguchi, T., Toyota, T., Adachi, H., Miyake, N., Matsumoto, N., Miyatake, S., Detecting a long insertion variant in SAMD12 by SMRT sequencing: implications of long-read whole-genome sequencing for repeat expansion diseases, J Hum Genet, 64 (2019), 191–7. DOI: https://doi.org/10.1038/s10038-018-0551-7.CrossRefGoogle ScholarPubMed
Niestroj, L. M., Perez-Palma, E., Howrigan, D. P., Zhou, Y., Cheng, F., Saarentaus, E., et al., Epilepsy subtype-specific copy number burden observed in a genome-wide study of 17 458 subjects, Brain, 143 (2020), 2106–18. DOI: https://doi.org/10.1093/brain/awaa171.Google Scholar
Epilepsy Phenome/Genome Project, Epi4K Consortium, Copy number variant analysis from exome data in 349 patients with epileptic encephalopathy, Ann Neurol, 78 (2015), 323–8. DOI: https://doi.org/10.1002/ana.24457.Google Scholar
Epi25 Collaborative, Ultra-rare genetic variation in the epilepsies: a whole-exome sequencing study of 17,606 individuals, Am J Hum Genet, 105 (2019), 267–82. DOI: https://doi.org/10.1016/j.ajhg.2019.05.020.Google Scholar
Zhang, L., Bai, W., Yuan, N., Du, Z., Comprehensively benchmarking applications for detecting copy number variation, PLoS Comput Biol, 15 (2019), e1007069. DOI: https://doi.org/10.1371/journal.pcbi.1007069.Google ScholarPubMed
Coe, B. P., Ylstra, B., Carvalho, B., Meijer, G. A., Macaulay, C., Lam, W. L. , Resolving the resolution of array CGH, Genomics, 89 (2007), 647–53. DOI: https://doi.org/10.1016/j.ygeno.2006.12.012.CrossRefGoogle ScholarPubMed
Zernant, J., Lee, W., Collison, F. T., Fishman, G. A., Sergeev, Y. V., Schuerch, K., et al., Frequent hypomorphic alleles account for a significant fraction of ABCA4 disease and distinguish it from age-related macular degeneration, J Med Genet, 54 (2017), 404–12. DOI: https://doi.org/10.1136/jmedgenet-2017-104540.Google Scholar
Castel, S. E., Cervera, A., Mohammadi, P., Aguet, F., Reverter, F., Wolman, A., et al., Modified penetrance of coding variants by cis-regulatory variation contributes to disease risk, Nat Genet, 50 (2018), 1327–34. DOI: https://doi.org/10.1038/s41588-018-0192-y.Google Scholar
Raj, B., Blencowe, B. J., Alternative splicing in the mammalian nervous system: recent insights into mechanisms and functional roles, Neuron, 87 (2015), 1427. DOI: https://doi.org/10.1016/j.neuron.2015.05.004.Google Scholar
Mele, M., Ferreira, P. G., Reverter, F., DeLuca, D. S., Monlong, J., Sammeth, M., et al., Human genomics. The human transcriptome across tissues and individuals, Science, 348 (2015), 660–5. DOI: https://doi.org/10.1126/science.aaa0355.Google Scholar
Uapinyoying, P., Goecks, J., Knoblach, S. M., Panchapakesan, K., Bonnemann, C. G., Partridge, T. A., et al., A new long-read RNA-seq analysis approach identifies and quantifies novel transcripts of very large genes, bioRxiv, 01.08.898627 (2020). DOI: https://doi.org/doi.org/10.1101/2020.01.08.898627.Google Scholar
Clark, M. B., Wrzesinski, T., Garcia, A. B., Hall, N. A. L., Kleinman, J. E., Hyde, T., et al., Long-read sequencing reveals the complex splicing profile of the psychiatric risk gene CACNA1C in human brain, Mol Psychiatry, 25 (2020), 3747. DOI: https://10.1038/s41380-019-0583-1.Google Scholar
Lim, J. S., Gopalappa, R., Kim, S. H., Ramakrishna, S., Lee, M., Kim, W. I., et al., Somatic mutations in TSC1 and TSC2 cause focal cortical dysplasia,Am J Hum Genet, 100 (2017), 454–72. DOI: https://doi.org/10.1016/j.ajhg.2017.01.030.CrossRefGoogle ScholarPubMed
Sim, N. S., Seo, Y., Lim, J. S., Kim, W. K., Son, H., Kim, H. D., et al., Brain somatic mutations in SLC35A2 cause intractable epilepsy with aberrant N-glycosylation, Neurol Genet, 4 (2018), e294. DOI: https://doi.org/10.1212/NXG.0000000000000294.Google Scholar
D’Gama, A. M., Woodworth, M. B., Hossain, A. A., Bizzotto, S., Hatem, N. E., LaCoursiere, C. M., et al., Somatic mutations activating the mTOR pathway in dorsal telencephalic progenitors cause a continuum of cortical dysplasias, Cell Rep, 21 (2017), 3754–66. DOI: https://doi.org/10.1016/j.celrep.2017.11.106.Google Scholar

Save element to Kindle

To save this element to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

How We Got to Where We're Going
Available formats
×

Save element to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

How We Got to Where We're Going
Available formats
×

Save element to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

How We Got to Where We're Going
Available formats
×