De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes
Open accessAbstract
Megalencephaly-capillary malformation (MCAP) and megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndromes are sporadic overgrowth disorders associated with markedly enlarged brain size and other recognizable features. We performed exome sequencing in 3 families with MCAP or MPPH, and our initial observations were confirmed in exomes from 7 individuals with MCAP and 174 control individuals, as well as in 40 additional subjects with megalencephaly, using a combination of Sanger sequencing, restriction enzyme assays and targeted deep sequencing. We identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. These include 2 mutations in AKT3, 1 recurrent mutation in PIK3R2 in 11 unrelated families with MPPH and 15 mostly postzygotic mutations in PIK3CA in 23 individuals with MCAP and 1 with MPPH. Our data highlight the central role of PI3K-AKT signaling in vascular, limb and brain development and emphasize the power of massively parallel sequencing in a challenging context of phenotypic and genetic heterogeneity combined with postzygotic mosaicism.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Somatic mutations identified in human hemimegalencephaly (HMG) reveal the dysregulated PI3K-AKT3-mTOR pathway as the causative mechanism.
“Somatic mutations that were identified in human hemimegalencephaly (HMG) revealed the dysregulated phosphoinositide 3-kinase (PI3K)–AKT3-mTOR pathway as the causative mechanism (Lee et al., 2012; Poduri et al., 2012; Riviere et al., 2012).”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Riviere et al., 2012
Additional somatic mutations causing HMG implicate key upstream and downstream components of the PI3K-AKT3-mTOR pathway, namely PI3K and mTOR.
“Additional somatic mutations causing HMG have been identified that implicate key upstream and downstream components of this pathway, namely PI3K and mTOR (Lee et al., 2012; Riviere et al., 2012).”
From Genetic Changes Shaping the Human Brain (2015) · cites this paper as Riviere et al., 2012
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041 · see citing works
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390 · see citing works
A framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,216 · see citing works
A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium (2010) · Nature · doi:10.1038/nature09534 · Cited by 7,877 · see citing works
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735 · see citing works
High Frequency of Mutations of the PIK3CA Gene in Human Cancers
Samuels, Y., Wang, Z., Bardelli, A., Silliman, N., Ptak, J., Szabo, S., Yan, H., Gazdar, A. F., Powell, S. M., Riggins, G. J., et al. (2004) · Science · doi:10.1126/science.1096502 · Cited by 3,448 · see citing works
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
Engelman, J. A., Luo, J., & Cantley, L. C. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1879 · Cited by 3,330 · see citing works
Amino Acid Difference Formula to Help Explain Protein Evolution
Grantham, R. L. (1974) · Science · doi:10.1126/science.185.4154.862 · Cited by 2,363 · see citing works
Liaw, D., Marsh, D. J., Li, J., Dahia, P. L. M., Wang, S. I., Zheng, Z., Bose, S., Call, K. M., Tsou, H. C., Peacoke, M., et al. (1997) · Nature Genetics · doi:10.1038/ng0597-64 · Cited by 2,083 · see citing works
Cho, H., Mu, J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Crenshaw, E. B., Kaestner, K. H., Bartolomei, M. S., Shulman, G. I., & Birnbaum, M. J. (2001) · Science · doi:10.1126/science.292.5522.1728 · Cited by 1,837 · see citing works
Synthesis and Function of 3-Phosphorylated Inositol Lipids
Vanhaesebroeck, B., Leevers, S. J., Ahmadi, K., Timms, J., Katso, R., Driscoll, P. C., Woscholski, R., Parker, P. J., & Waterfield, M. D. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.535 · Cited by 1,535 · see citing works
Brownstein, M., Carpten, J. D., & Smith, J. R. (1996) · BioTechniques · doi:10.2144/96206st01 · Cited by 1,287 · see citing works
Akt signalling in health and disease
Hers, I., Vincent, E. E., & Tavaré, J. M. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2011.05.004 · Cited by 1,246 · see citing works
Katso, R., Okkenhaug, K., Ahmadi, K., White, S., Timms, J. F., & Waterfield, M. D. (2001) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.17.1.615 · Cited by 1,204 · see citing works
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations
O'Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., Karakoc, E., MacKenzie, A. P., Ng, S. B., Baker, C., et al. (2011) · Nature Genetics · doi:10.1038/ng.835 · Cited by 1,203 · see citing works
Self-citationHigh-throughput oncogene mutation profiling in human cancer
Thomas, R. K., Baker, A. C., Debiasi, R. M., Winckler, W., LaFramboise, T., Lin, W. M., Wang, M., Feng, W., Zander, T., MacConaill, L. E., et al. (2007) · Nature Genetics · doi:10.1038/ng1975 · Cited by 978 · see citing works
Cho, H., Thorvaldsen, J. L., Chu, Q., Feng, F., & Birnbaum, M. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100462200 · Cited by 959 · see citing works
The Biology and Clinical Relevance of the PTEN Tumor Suppressor Pathway
Sansal, I., & Sellers, W. R. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.02.141 · Cited by 922 · see citing works
A Mosaic Activating Mutation in AKT1 Associated with the Proteus Syndrome
Lindhurst, M. J., Sapp, J. C., Teer, J. K., Johnston, J. J., Finn, E., Peters, K. F., Turner, J. T., Cannons, J. L., Bick, D. P., Blakemore, L. C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1104017 · Cited by 892 · see citing works
PDK1, the master regulator of AGC kinase signal transduction
Mora, A., Komander, D., van Aalten, D. M. F., & Alessi, D. R. (2004) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2003.12.022 · Cited by 802 · see citing works
Rate, molecular spectrum, and consequences of human mutation
Lynch, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912629107 · Cited by 792 · see citing works
Butler, M. G., Dasouki, M. J., Zhou, X.-P., Talebizadeh, Z., Brown, M., Takahashi, T. N., Miles, J. H., Wang, C. H., Stratton, R., Pilarski, R., et al. (2005) · Journal of Medical Genetics · doi:10.1136/jmg.2004.024646 · Cited by 778 · see citing works
Otsu, M., Hiles, I., Gout, I. T., Fry, M., Ruiz‐Larrea, F., Panayotou, G., Thompson, A., Dhand, R., Hsuan, J. J., Totty, N. F., et al. (1991) · Cell · doi:10.1016/0092-8674(91)90411-q · Cited by 764 · see citing works
Marsh, D. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.3.507 · Cited by 653 · see citing works
A Family with Severe Insulin Resistance and Diabetes Due to a Mutation in AKT2
George, S., Rochford, J. J., Wolfrum, C., Gray, S. L., Schinner, S., Wilson, J. C., Soos, M. A., Murgatroyd, P. R., Williams, R. M., Acerini, C. L., et al. (2004) · Science · doi:10.1126/science.1096706 · Cited by 559 · see citing works
Happle, R. (1987) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(87)80249-9 · Cited by 554 · see citing works
Targeting phosphoinositide 3-kinase—Moving towards therapy
Marone, R., Cmiljanović, V., Giese, B., & Wymann, M. P. (2007) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.10.003 · Cited by 548 · see citing works
Oncogenic PI3K and its role in cancer
Samuels, Y., & Ericson, K. M. (2005) · Current Opinion in Oncology · doi:10.1097/01.cco.0000198021.99347.b9 · Cited by 519 · see citing works
Somatic activation of AKT3 causes hemispheric developmental brain malformations
Poduri, A., Evrony, G. D., Cai, X., Elhosary, P. C., Beroukhim, R., Lehtinen, M. K., Hills, L. B., Heinzen, E. L., Hill, A., Hill, R. S., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.010 · Cited by 478 · see citing works
Cheung, L. W. T., Hennessy, B. T., Li, J., Yu, S., Myers, A. P., Djordjevic, B., Lu, Y., Stemke‐Hale, K., Dyer, M. D., Zhang, F., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0039 · Cited by 471 · see citing works
Tschopp, O., Yang, Z.-Z., Brodbeck, D., Dummler, B. A., Hemmings-Mieszczak, M., Watanabe, T., Michaelis, T., Frahm, J., & Hemmings, B. A. (2005) · Development · doi:10.1242/dev.01864 · Cited by 414 · see citing works
Rare cancer-specific mutations in PIK3CA show gain of function
Gymnopoulos, M., Elsliger, M., & Vogt, P. K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701005104 · Cited by 378 · see citing works
Functional Analysis of PIK3CA Gene Mutations in Human Colorectal Cancer
Ikenoue, T., Kanai, F., Hikiba, Y., Obata, T., Tanaka, Y., Imamura, J., Ohta, M., Jazag, A., Guleng, B., Tateishi, K., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4114 · Cited by 366 · see citing works
De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome
Rivière, J., van Bon, B. W. M., Hoischen, A., Kholmanskikh, S. S., O’Roak, B. J., Gilissen, C., Gijsen, S. J., Sullivan, C. T., Christian, S. L., Abdul-Rahman, O. A., et al. (2012) · Nature Genetics · doi:10.1038/ng.1091 · Cited by 303 · see citing works
Self-citationSomatic Mutations in p85α Promote Tumorigenesis through Class IA PI3K Activation
Jaiswal, B. S., Janakiraman, V., Kljavin, N. M., Chaudhuri, S., Stern, H. M., Wang, W., Kan, Z., Dbouk, H. A., Peters, B. A., Waring, P., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.10.016 · Cited by 288 · see citing works
Mirzaa, G., Conway, R. L., Gripp, K. W., Lerman‐Sagie, T., Siegel, D. H., de Vries, L. S., Lev, D., Kramer, N., Hopkins, E., Graham, J. M., et al. (2012) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.34402 · Cited by 239 · see citing works
Self-citationBrodbeck, D., Cron, P. D., & Hemmings, B. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.14.9133 · Cited by 204 · see citing works
Oda, K., Okada, J., Timmerman, L., Rodriguez‐Viciana, P., Stokoe, D., Shoji, K., Taketani, Y., Kuramoto, H., Knight, Z. A., Shokat, K. M., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0755 · Cited by 189 · see citing works
Phosphatidylinositol 3‐kinase inhibitors: promising drug candidates for cancer therapy
Kong, D., & Yamori, T. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00891.x · Cited by 180 · see citing works
An Activating Mutation of AKT2 and Human Hypoglycemia
Hussain, K., Challis, B., Rocha, N., Payne, F., Minic, M., Thompson, A., Daly, A., Scott, C. L., Harris, J. R., Smillie, B. J. L., et al. (2011) · Science · doi:10.1126/science.1210878 · Cited by 178 · see citing works
Single-nucleotide evolutionary constraint scores highlight disease-causing mutations
Cooper, G. M., Goode, D. L., Ng, S. B. H., Sidow, A., Bamshad, M. J., Shendure, J., & Nickerson, D. A. (2010) · Nature Methods · doi:10.1038/nmeth0410-250 · Cited by 171 · see citing works
Self-citationBoland, E., Clayton‐Smith, J., Woo, V. G. H., McKee, S. A., Manson, F. D. C., Medne, L., Zackai, E. H., Swanson, E. A., FitzPatrick, D. R., Millen, K. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519999 · Cited by 168 · see citing works
Self-citationBallif, B. C., Rosenfeld, J. A., Traylor, R. N., Theisen, A. P., Bader, P. I., Ladda, R. L., Sell, S. L., Steinraths, M., Surti, U., McGuire, M., et al. (2011) · Human Genetics · doi:10.1007/s00439-011-1073-y · Cited by 150 · see citing works
Macrocephaly with cutis marmorata, haemangioma and syndactyly ??? a distinctive overgrowth syndrome
Clayton‐Smith, J., Kerr, B. A., Brunner, H. G., Tranebjærg, L., Magee, A. J., Hennekam, R. C. M., Mueller, R. F., Brueton, L. A., Super, M., Steen-Johnsen, J., et al. (1997) · Clinical Dysmorphology · doi:10.1097/00019605-199710000-00001 · Cited by 127 · see citing works
Neuroimaging findings in macrocephaly–capillary malformation: A longitudinal study of 17 patients
Conway, R. L., Pressman, B. D., Dobyns, W. B., Danielpour, M., Lee, J., Sanchez-Lara, P. A., Butler, M. G., Zackai, E. H., Lindsey, C., Saitta, S. C., et al. (2007) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32040 · Cited by 118 · see citing works
Self-citationDeletions of 20p12 in Alagille syndrome: Frequency and molecular characterization
Krantz, I. D., Rand, E. B., Genin, A., Hunt, P., Jones, M. C., Louis, A. A., Graham, J. M., Bhatt, S., Piccoli, D. A., & Spinner, N. B. (1997) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19970502)70:1 · Cited by 117 · see citing works
Self-citationScarano, E., Iaccarino, M., Grippo, P., & Parisi, E. (1967) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.57.5.1394 · Cited by 94 · see citing works
Volinia, S., Hiles, I. D., Ormondroyd, E., Nižetić, D., Antonacci, R., Rocchi, M., & Waterfield, M. D. (1994) · Genomics · doi:10.1006/geno.1994.1655 · Cited by 93 · see citing works
A novel Akt3 mutation associated with enhanced kinase activity and seizure susceptibility in mice
Tokuda, S., Mahaffey, C. L., Monks, B., Faulkner, C., Birnbaum, M. J., Danzer, S. C., & Frankel, W. N. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq544 · Cited by 69 · see citing works
Mirzaa, G., Dodge, N. N., Glass, I. A., Day, C. S., Gripp, K. W., Nicholson, L., Straub, V. W., Voït, T., & Dobyns, W. B. (2004) · Neuropediatrics · doi:10.1055/s-2004-830497 · Cited by 68 · see citing works
Self-citationKong, S., Ki, C., Yoo, B. C., & Kim, J. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2007.00693.x · Cited by 63 · see citing works
Gripp, K. W., Hopkins, E., Vinkler, C., Lev, D., Malinger, G., Lerman‐Sagie, T., & Dobyns, W. B. (2009) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32732 · Cited by 36 · see citing works
Self-citationA proposal for classification of entities combining vascular malformations and deregulated growth
Oduber, C. E. U., van der Horst, C. M. A. M., Smitt, J. H. S., Smeulders, M. J. C., Mendiratta, V., Harper, J. I., Steensel, M. A. M. V., & Hennekam, R. C. M. (2011) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2011.02.007 · Cited by 22 · see citing works
Flagged first, then by citations
1 of the 55 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
PI3K and cancer: lessons, challenges and opportunities
Fruman, D. A., & Rommel, C. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4204 · Cited by 1,716 · see citing works
PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting
Thorpe, L. M., Yuzugullu, H., & Zhao, J. J. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3860 · Cited by 1,365 · see citing works
Rare-disease genetics in the era of next-generation sequencing: discovery to translation
Boycott, K. M., Vanstone, M. R., Bulman, D. E., & MacKenzie, A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3555 · Cited by 764 · see citing works
Self-citationGenetic studies in intellectual disability and related disorders
Vissers, L. E. L. M., Gilissen, C., & Veltman, J. A. (2016) · Nature Reviews Genetics · doi:10.1038/nrg3999 · Cited by 761 · see citing works
Lipton, J. O., & Şahin, M. (2014) · Neuron · doi:10.1016/j.neuron.2014.09.034 · Cited by 711 · see citing works
The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities
Chong, J. X., Buckingham, K. J., Jhangiani, S. N., Boehm, C., Sobreira, N., Smith, J. D., Harrell, T. M., McMillin, M. J., Wiszniewski, W., Gambin, T., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.06.009 · Cited by 643 · see citing works
Self-citationA genomic view of mosaicism and human disease
Biesecker, L. G., & Spinner, N. B. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3424 · Cited by 623 · see citing works
Somatic mutation, genomic variation, and neurological disease
Poduri, A., Evrony, G. D., Cai, X., & Walsh, C. A. (2013) · Science · doi:10.1126/science.1237758 · Cited by 584 · see citing works
Keppler‐Noreuil, K. M., Rios, J. J., Parker, V., Semple, R. K., Lindhurst, M. J., Sapp, J. C., Alomari, A. I., Ezaki, M., Dobyns, W. B., & Biesecker, L. G. (2014) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36836 · Cited by 583 · see citing works
Self-citationLuks, V. L., Kamitaki, N., Vivero, M. P., Uller, W., Rab, R., Bovée, J. V. M. G., Rialon, K. L., Guevara, C. J., Alomari, A. I., Greene, A. K., et al. (2015) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2014.12.069 · Cited by 580 · see citing works
Self-citationSingle-Neuron Sequencing Analysis of L1 Retrotransposition and Somatic Mutation in the Human Brain
Evrony, G. D., Cai, X., Lee, E., Hills, L. B., Elhosary, P. C., Lehmann, H. S., Parker, J. J., Atabay, K. D., Gilmore, E. C., Poduri, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.09.035 · Cited by 548 · see citing works
Liang, Q., Luo, Z., Zeng, J., Chen, W., Foo, S., Lee, S.-A., Ge, J., Wang, S., Goldman, S. A., Zloković, B. V., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.07.019 · Cited by 538 · see citing works
Lim, J. S., Kim, W.-I., Kang, H., Kim, S. H., Park, A. H., Park, E. K., Cho, Y., Kim, H. M., Kim, J. A., Kim, J. A., et al. (2015) · Nature Medicine · doi:10.1038/nm.3824 · Cited by 524 · see citing works
Malformations of cortical development: clinical features and genetic causes
Guerrini, R., & Dobyns, W. B. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70040-7 · Cited by 513 · see citing works
Self-citationGrowth and folding of the mammalian cerebral cortex: from molecules to malformations
Sun, T., & Hevner, R. F. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3707 · Cited by 471 · see citing works
New insights into the generation and role of de novo mutations in health and disease
Acuña‐Hidalgo, R., Veltman, J. A., & Hoischen, A. (2016) · Genome biology · doi:10.1186/s13059-016-1110-1 · Cited by 451 · see citing works
Induction of Expansion and Folding in Human Cerebral Organoids
Li, Y., Muffat, J., Omer, A., Bosch, I., Lancaster, M. A., Sur, M., Gehrke, L., Knoblich, J. A., & Jaenisch, R. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2016.11.017 · Cited by 436 · see citing works
Somatic mutations in cerebral cortical malformations
Jamuar, S. S., Lam, A.-T. N., Kircher, M., D’Gama, A. M., Wang, J., Barry, B. J., Zhang, X., Hill, R. S., Partlow, J. N., Rozzo, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1314432 · Cited by 392 · see citing works
Self-citationNajm, I., Lal, D., Alonso‐Vanegas, M., Cendes, F., Lopes‐Cendes, Í., Palmini, A., Paglioli, E., Sarnat, H. B., Walsh, C. A., Wiebe, S., et al. (2022) · Epilepsia · doi:10.1111/epi.17301 · Cited by 368 · see citing works
Cerebral cortex expansion and folding: what have we learned?
Fernández, V., Llinares-Benadero, C., & Borrell, V. (2016) · The EMBO Journal · doi:10.15252/embj.201593701 · Cited by 357 · see citing works
Jansen, L. A., Mirzaa, G. M., Ishak, G. E., O'Roak, B. J., Hiatt, J. B., Roden, W. H., Gunter, S. A., Christian, S. L., Collins, S., Adams, C., et al. (2015) · Brain · doi:10.1093/brain/awv045 · Cited by 364 · see citing works
Self-citationTargeted capture in evolutionary and ecological genomics
Jones, M. R., & Good, J. M. (2015) · Molecular Ecology · doi:10.1111/mec.13304 · Cited by 350 · see citing works
Somatic Activating PIK3CA Mutations Cause Venous Malformation
Limaye, N., Kangas, J., Mendola, A., Godfraind, C., Schlögel, M. J., Helaers, R., Eklund, L., Boon, L. M., & Vikkula, M. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.11.011 · Cited by 350 · see citing works
Hiatt, J. B., Pritchard, C. C., Salipante, S. J., O’Roak, B. J., & Shendure, J. (2013) · Genome Research · doi:10.1101/gr.147686.112 · Cited by 325 · see citing works
Self-citationPhosphatidylinositol 3-kinase, growth disorders, and cancer
Goncalves, M. D., Hopkins, B. D., & Cantley, L. C. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1704560 · Cited by 327 · see citing works
Clinical delineation and natural history of the PIK3CA ‐related overgrowth spectrum
Keppler‐Noreuil, K. M., Sapp, J. C., Lindhurst, M. J., Parker, V., Blumhorst, C., Darling, T. N., Tosi, L. L., Huson, S., Whitehouse, R. W., Jakkula, E., et al. (2014) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36552 · Cited by 305 · see citing works
Self-citationLucas, C. L., Zhang, Y., Venida, A. C., Wang, Y., Hughes, J. D., McElwee, J. J., Butrick, M., Matthews, H. F., Price, S. M., Biancalana, M., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20141759 · Cited by 295 · see citing works
Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy
Al-Olabi, L., Polubothu, S., Dowsett, K., Andrews, K. A., Stadnik, P., Joseph, A. P., Knox, R. G., Pittman, A. M., Clark, G. R., Baird, W., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci98589 · Cited by 293 · see citing works
Self-citationD’Gama, A. M., Geng, Y., Couto, J. A., Martin, B., Boyle, E. A., LaCoursiere, C. M., Hossain, A. A., Hatem, N. E., Barry, B. J., Kwiatkowski, D. J., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24357 · Cited by 290 · see citing works
Self-citationCancer-Associated PIK3CA Mutations in Overgrowth Disorders
Madsen, R. R., Vanhaesebroeck, B., & Semple, R. K. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.08.003 · Cited by 276 · see citing works
Structural Basis for Regulation of Phosphoinositide Kinases and Their Involvement in Human Disease
Burke, J. E. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.08.005 · Cited by 276 · see citing works
Mirzaa, G., Campbell, C., Solovieff, N., Goold, C. P., Jansen, L., Menon, S., Timms, A., Conti, V., Biag, J., Adams, C., et al. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.0363 · Cited by 246 · see citing works
Self-citationSomatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies
Keppler‐Noreuil, K. M., Parker, V. E. R., Darling, T. N., & Martinez‐Agosto, J. A. (2016) · American Journal of Medical Genetics Part C: Seminars in Medical Genetics · doi:10.1002/ajmg.c.31531 · Cited by 270 · see citing works
Turner, T. N., Hormozdiari, F., Duyzend, M., McClymont, S. A., Hook, P. W., Iossifov, I. H., Raja, A. N., Baker, C. A., Hoekzema, K., Stessman, H. A. F., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.11.023 · Cited by 263 · see citing works
McConnell, M. J., Moran, J. V., Abyzov, A., Akbarian, S., Bae, T., Cortes-Ciriano, I., Erwin, J. A., Fasching, L., Flasch, D. A., Freed, D., et al. (2017) · Science · doi:10.1126/science.aal1641 · Cited by 262 · see citing works
Translation deregulation in human disease
Tahmasebi, S., Khoutorsky, A., Mathews, M. B., & Sonenberg, N. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0034-x · Cited by 255 · see citing works
Advancing epilepsy genetics in the genomic era
Myers, C. T., & Mefford, H. C. (2015) · Genome Medicine · doi:10.1186/s13073-015-0214-7 · Cited by 247 · see citing works
Deconstructing cortical folding: genetic, cellular and mechanical determinants
Llinares-Benadero, C., & Borrell, V. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0112-2 · Cited by 243 · see citing works
Somatic mosaicism and neurodevelopmental disease
D’Gama, A. M., & Walsh, C. A. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0257-3 · Cited by 236 · see citing works
FORGE Canada Consortium: Outcomes of a 2-Year National Rare-Disease Gene-Discovery Project
Beaulieu, C. L., Majewski, J., Schwartzentruber, J., Samuels, M. E., Fernandez, B. A., Bernier, F. P., Brudno, M., Knoppers, B. M., Marcadier, J., Dyment, D. A., et al. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.05.003 · Cited by 239 · see citing works
Self-citationGenetic Basis and Therapies for Vascular Anomalies
Queisser, A., Seront, E., Boon, L. M., & Vikkula, M. (2021) · Circulation Research · doi:10.1161/circresaha.121.318145 · Cited by 237 · see citing works
Novel genetic loci underlying human intracranial volume identified through genome-wide association
Adams, H., Hibar, D., Chouraki, V., Stein, J., Nyquist, P., Rentería, M. E., Trompet, S., Arias-Vásquez, A., Seshadri, S., Desriviéres, S., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4398 · Cited by 238 · see citing works
SHP2 sails from physiology to pathology
Tajan, M., de Rocca Serra, A., Valet, P., Edouard, T., & Yart, A. (2015) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2015.08.005 · Cited by 232 · see citing works
Somatic Activating Mutations in GNAQ and GNA11 Are Associated with Congenital Hemangioma
Ayturk, U. M., Couto, J. A., Hann, S., Mulliken, J. B., Williams, K. L., Huang, A. Y., Fishman, S. J., Boyd, T. K., Kozakewich, H. P., Bischoff, J. E., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.03.009 · Cited by 221 · see citing works
Klippel–Trenaunay syndrome belongs to the PIK3CA‐related overgrowth spectrum (PROS)
Vahidnezhad, H., Youssefian, L., & Uitto, J. (2015) · Experimental Dermatology · doi:10.1111/exd.12826 · Cited by 217 · see citing works
Synergy in activating class I PI3Ks
Burke, J. E., & Williams, R. L. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.12.003 · Cited by 216 · see citing works
Somatic PIK3CA mutations as a driver of sporadic venous malformations
Castel, P., Carmona, F. J., Grego‐Bessa, J., Berger, M. F., Viale, A. J., Anderson, K. V., Bagué, S., Scaltriti, M., Antonescu, C. R., Baselga, E., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf1164 · Cited by 213 · see citing works
Genetic Basis of Brain Malformations
Parrini, E., Conti, V., Dobyns, W. B., & Guerrini, R. (2016) · Molecular Syndromology · doi:10.1159/000448639 · Cited by 210 · see citing works
Self-citationMicroglia Mediated Neuroinflammation: Focus on PI3K Modulation
Cianciulli, A., Porro, C., Calvello, R., Trotta, T., Lofrumento, D. D., & Panaro, M. A. (2020) · Biomolecules · doi:10.3390/biom10010137 · Cited by 210 · see citing works
PI3K Signaling in Neurons: A Central Node for the Control of Multiple Functions
Sánchez‐Alegría, K., Flores‐León, M., Ávila-Muñoz, E., Rodríguez-Corona, N., & Arias, C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123725 · Cited by 209 · see citing works
Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder
Krupp, D. R., Barnard, R. A., Duffourd, Y., Evans, S. A., Mulqueen, R. M., Bernier, R., Rivière, J.-B., Fombonne, E., & O’Roak, B. J. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.07.016 · Cited by 204 · see citing works
Self-citationPIK3R1 Mutations Cause Syndromic Insulin Resistance with Lipoatrophy
Thauvin‐Robinet, C., Auclair, M., Duplomb, L., Caron, M., Avila, M., St‐Onge, J., Merrer, M. F. L., Luyer, B. L., Héron, D., Mathieu‐Dramard, M., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.05.019 · Cited by 203 · see citing works
Self-citationGermline PIK3CA and AKT1 mutations in cowden and cowden-like syndromes
Orloff, M. S., He, X., Peterson, C., Chen, F., Chen, J.-L., Mester, J. L., & Eng, C. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.10.021 · Cited by 201 · see citing works
Somatic Mutations in the MTOR gene cause focal cortical dysplasia type IIb
Nakashima, M., Saitsu, H., Takei, N., Tohyama, J., Kato, M., Kitaura, H., Shiina, M., Shirozu, H., Masuda, H., Watanabe, K., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24444 · Cited by 184 · see citing works
Mutations in PIK3R1 Cause SHORT Syndrome
Dyment, D. A., Smith, A. C., Alcantara, D., Schwartzentruber, J., Basel‐Vanagaite, L., Curry, C. J., Temple, I. K., Reardon, W., Mansour, S., Haq, M. R., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.06.005 · Cited by 197 · see citing works
Self-citationSomatic activating mutations in Pik3ca cause sporadic venous malformations in mice and humans
Castillo, S. D., Tzouanacou, E., Thin, M. Z., Berenjeno, I. M., Parker, V., Chivite, Í., Milà‐Guasch, M., Pearce, W. P., Solomon, I., Angulo‐Urarte, A., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad9982 · Cited by 190 · see citing works
Thomas, A. C., Zeng, Z., Rivière, J., O’Shaughnessy, R. F. L., Al-Olabi, L., St‐Onge, J., Atherton, D. J., Aubert, H., Bagazgoitia, L., Barbarot, S., et al. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2015.11.027 · Cited by 191 · see citing works
Self-citationRoles of PI3K/AKT/GSK3 Pathway Involved in Psychiatric Illnesses
Matsuda, S., Ikeda, Y., Murakami, M., Nakagawa, Y., Tsuji, A., & Kitagishi, Y. (2019) · Diseases · doi:10.3390/diseases7010022 · Cited by 189 · see citing works
Mirzaa, G., Timms, A. E., Conti, V., Boyle, E. A., Girisha, K. M., Martin, B., Kircher, M., Olds, C., Juusola, J., Collins, S., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.87623 · Cited by 184 · see citing works
Self-citationmTOR Signaling in Epilepsy: Insights from Malformations of Cortical DevelopmentPreprint
Crino, P. B. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a022442 · Cited by 184 · see citing works
NGS Technologies as a Turning Point in Rare Disease Research , Diagnosis and Treatment
Marmiesse, A. F., Gouveia, S., & Couce, M. L. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666170718101946 · Cited by 180 · see citing works
Wang, L., Zhou, K., Fu, Z., Yu, D., Huang, H., Zang, X., & Mo, X. (2017) · Journal of Molecular Neuroscience · doi:10.1007/s12031-016-0872-y · Cited by 172 · see citing works
The Diverse Genetic Landscape of Neurodevelopmental Disorders
Hu, W. F., Chahrour, M. H., & Walsh, C. A. (2014) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090413-025600 · Cited by 169 · see citing works
Megalencephaly Syndromes and Activating Mutations in the PI3K‐AKT Pathway: MPPH and MCAP
Mirzaa, G., Rivière, J., & Dobyns, W. B. (2013) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31361 · Cited by 171 · see citing works
Self-citationRAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes
Reijnders, M. R. F., Ansor, N. M., Kousi, M., Yue, W. W., Tan, P. L., Clarkson, K., Clayton-Smith, J., Corning, K., Jones, J. R., Lam, W. W. K., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.08.007 · Cited by 168 · see citing works
Self-citationConnell, F., Gordon, K. D., Brice, G. W., Keeley, V. L., Jeffery, S., Mortimer, P. S., Mansour, S., & Østergaard, P. (2013) · Clinical Genetics · doi:10.1111/cge.12173 · Cited by 167 · see citing works
Somatic gain-of-function mutations in PIK3CA in patients with macrodactyly
Rios, J. J., Paria, N., Burns, D. K., Israel, B. A., Cornelia, R., Wise, C. A., & Ezaki, M. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds440 · Cited by 167 · see citing works
Malformations of Cortical Development and EpilepsyPreprint
Barkovich, A. J., Dobyns, W. B., & Guerrini, R. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a022392 · Cited by 160 · see citing works
Self-citationSHORT Syndrome with Partial Lipodystrophy Due to Impaired Phosphatidylinositol 3 Kinase Signaling
Chudasama, K., Winnay, J. N., Johansson, S., Claudi, T., König, R., Haldorsen, I. S., Johansson, B. B., Woo, J. R., Aarskog, D., Sagen, J. V., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.05.023 · Cited by 158 · see citing works
Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum
Parker, V., Keppler‐Noreuil, K. M., Faivre, L. O., Luu, M., Oden, N. L., Silva, L. D., Sapp, J. C., Andrews, K. A., Bardou, M., Chen, K. Y., et al. (2018) · Genetics in Medicine · doi:10.1038/s41436-018-0297-9 · Cited by 158 · see citing works
Jin, S. C., Dong, W., Kundishora, A. J., Panchagnula, S., Moreno-De-Luca, A., Furey, C. G., Allocco, A. A., Walker, R. L., Nelson-Williams, C. J., Smith, H. L., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1090-2 · Cited by 156 · see citing works
Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms
D’Gama, A. M., Pochareddy, S., Li, M., Jamuar, S. S., Rodin, R. E., Lam, A.-T. N., Šestan, N., & Walsh, C. A. (2015) · Neuron · doi:10.1016/j.neuron.2015.11.009 · Cited by 149 · see citing works
Somatic activating mutations in PIK3CA cause generalized lymphatic anomaly
Rodríguez‐Laguna, L., Agrá, N., Ibañez, K., Oliva-Molina, G., Gordo, G., Khurana, N., Hominick, D., Beato, M., Colmenero, I., Herranz, G., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20181353 · Cited by 154 · see citing works
Recent advances in the molecular genetics of epilepsy
Hildebrand, M. S., Dahl, H. M., Damiano, J. A., Smith, R. J. H., Scheffer, I. E., & Berkovic, S. F. (2013) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2012-101448 · Cited by 148 · see citing works
Somatic Mosaicism in the Human Genome
Freed, D. N., Stevens, E. L., & Pevsner, J. (2014) · Genes · doi:10.3390/genes5041064 · Cited by 150 · see citing works
Marangi, G., & Traynor, B. J. (2014) · Brain Research · doi:10.1016/j.brainres.2014.10.009 · Cited by 148 · see citing works
Molecules in medicine mini-review: isoforms of PI3K in biology and disease
Vanhaesebroeck, B., Whitehead, M. A., & Piñeiro, R. (2015) · Journal of Molecular Medicine · doi:10.1007/s00109-015-1352-5 · Cited by 147 · see citing works
Oegema, R., Barakat, T. S., Wilke, M., Stouffs, K., Amrom, D., Aronica, E., Bahi‐Buisson, N., Conti, V., Fry, A. E., Geis, T., et al. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0395-6 · Cited by 147 · see citing works
Self-citationMirzaa, G., Parry, D. A., Fry, A. E., Giamanco, K. A., Schwartzentruber, J., Vanstone, M. R., Logan, C. V., Roberts, N. Y., Johnson, C. A., Singh, S., et al. (2014) · Nature Genetics · doi:10.1038/ng.2948 · Cited by 148 · see citing works
Self-citationMalformations of cortical development
Desikan, R. S., & Barkovich, A. J. (2016) · Annals of Neurology · doi:10.1002/ana.24793 · Cited by 146 · see citing works
Boscolo, E., Coma, S., Luks, V. L., Greene, A. K., Klagsbrun, M., Warman, M. L., & Bischoff, J. E. (2014) · Angiogenesis · doi:10.1007/s10456-014-9453-2 · Cited by 142 · see citing works
Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3
Sim, J. C. H., Scerri, T., Fanjul-Fernández, M., Riseley, J. R., Gillies, G., Pope, K., van Roozendaal, H., Heng, J., Mandelstam, S., McGillivray, G., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24502 · Cited by 135 · see citing works
Kawasaki, Y., Oda, H., Ito, J., Niwa, A., Tanaka, T., Hijikata, A., Seki, R., Nagahashi, A., Osawa, M., Asaka, I., et al. (2016) · Arthritis & Rheumatology · doi:10.1002/art.39960 · Cited by 137 · see citing works
Megalencephaly and hemimegalencephaly: Breakthroughs in molecular etiology
Mirzaa, G., & Poduri, A. (2014) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31401 · Cited by 136 · see citing works
Self-citationMidbrain and hindbrain malformations: advances in clinical diagnosis, imaging, and genetics
Doherty, D., Millen, K. J., & Barkovich, A. J. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70024-3 · Cited by 137 · see citing works
Genetic Changes Shaping the Human Brain
Bae, B.-I., Jayaraman, D., & Walsh, C. A. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.01.035 · Cited by 135 · see citing works
High rate of mosaicism in individuals with Cornelia de Lange syndrome
Huisman, S. A., Redeker, E. J. W., Maas, S. M., Mannens, M. M. A. M., & Hennekam, R. C. M. (2013) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2012-101477 · Cited by 137 · see citing works
Rathinaswamy, M. K., & Burke, J. E. (2019) · Advances in Biological Regulation · doi:10.1016/j.jbior.2019.100657 · Cited by 140 · see citing works
Kuentz, P., St‐Onge, J., Duffourd, Y., Courcet, J., Carmignac, V., Jouan, T., Sorlin, A., Abasq‐Thomas, C., Albuisson, J., Amiel, J., et al. (2017) · Genetics in Medicine · doi:10.1038/gim.2016.220 · Cited by 131 · see citing works
Self-citationPolymicrogyria: A common and heterogeneous malformation of cortical development
Stutterd, C., & Leventer, R. J. (2014) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31399 · Cited by 128 · see citing works
study, D. D. D., Broix, L., Jagline, H., Ivanova, E. L., Schmucker, S., Drouot, N., Clayton‐Smith, J., Pagnamenta, A. T., Metcalfe, K., Isidor, B., et al. (2016) · Nature Genetics · doi:10.1038/ng.3676 · Cited by 126 · see citing works
Genetics and mechanisms leading to human cortical malformations
Romero, D. M., Bahi‐Buisson, N., & Francis, F. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.09.031 · Cited by 126 · see citing works
Hall, J. G., Aldinger, K. A., & Tanaka, K. I. (2014) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36395 · Cited by 126 · see citing works
Epilepsy in the mTORopathies: opportunities for precision medicine
Moloney, P. B., Cavalleri, G. L., & Delanty, N. (2021) · Brain Communications · doi:10.1093/braincomms/fcab222 · Cited by 126 · see citing works
The Genetic Basis of Hydrocephalus
Kousi, M., & Katsanis, N. (2016) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070815-014023 · Cited by 124 · see citing works
The categories of cutaneous mosaicism: A proposed classification
Happle, R. (2015) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37439 · Cited by 123 · see citing works
Baek, S. T., Copeland, B. R., Yun, E.-J., Kwon, S., Guemez‐Gamboa, A., Schaffer, A. E., Kim, S., Kang, H., Song, S., Mathern, G. W., et al. (2015) · Nature Medicine · doi:10.1038/nm.3982 · Cited by 122 · see citing works
let-7 and miR-140 microRNAs coordinately regulate skeletal development
Papaioannou, G., Inloes, J. B., Nakamura, Y., Paltrinieri, E., & Kobayashi, T. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1302797110 · Cited by 118 · see citing works
Malformations of Cerebral Cortex Development: Molecules and Mechanisms
Juric‐Sekhar, G., & Hevner, R. F. (2019) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012927 · Cited by 116 · see citing works
A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR– B cells
Boisson, B., Wang, Y., Bosompem, A., Ma, C. S., Lim, A., Kochetkov, T., Tangye, S. G., Casanova, J., & Conley, M. E. (2013) · Journal of Clinical Investigation · doi:10.1172/jci71927 · Cited by 116 · see citing works
- Authors
- Finding of Rare Disease Genes (FORGE) Canada Consortium, Rivière, J.-B., Mirzaa, G. M., O'Roak, B. J., Beddaoui, M., Alcantara, D., Conway, R. L., St-Onge, J., Schwartzentruber, J. A., Gripp, K. W., Nikkel, S. M., Worthylake, T., Sullivan, C. T., Ward, T. R., Butler, H. E., Kramer, N. A., Albrecht, B., Armour, C. M., Armstrong, L., Caluseriu, O., Cytrynbaum, C., Drolet, B. A., Innes, A. M., Lauzon, J. L., Lin, A. E., Mancini, G. M. S., Meschino, W. S., Reggin, J. D., Saggar, A. K., Lerman-Sagie, T., Uyanik, G., Weksberg, R., Zirn, B., Beaulieu, C. L., Majewski, J., Bulman, D. E., O'Driscoll, M., Shendure, J., Graham, J. M., Boycott, K. M., & Dobyns, W. B.
- Affiliations
- Seattle Children's Hospital (US)
- University of Chicago (US)
- University of Ottawa (CA)
- University of Sussex (GB)
- Michigan State University (US)
- McGill University and Génome Québec Innovation Centre (CA)
- Alfred I. duPont Hospital for Children (US)
- Children's Hospital of Eastern Ontario (CA)
- Cedars-Sinai Medical Center (US)
- Essen University Hospital (DE)
- Queen's University (CA)
- University of British Columbia (CA)
- University of Calgary (CA)
- Hospital for Sick Children (CA)
- Medical College of Wisconsin (US)
- Massachusetts General Hospital (US)
- Erasmus MC (NL)
- North York General Hospital (CA)
- Providence Sacred Heart Medical Center (US)
- University of London (GB)
- University of Göttingen (DE)
- McGill University (CA)
- University of Washington (US)
- Corresponding author
- Dobyns, William B
- ORCID
- Rivière, Jean-Baptiste
- Mirzaa, Ghayda M
- Alcantara, Diana
- Schwartzentruber, Jeremy A
- Gripp, Karen W
- Nikkel, Sarah M
- Armour, Christine M
- Armstrong, Linlea
- Caluseriu, Oana
- Cytrynbaum, Cheryl
- Drolet, Beth A
- Innes, A Micheil
- Lin, Angela E
- Mancini, Grazia M S
- Weksberg, Rosanna
- Zirn, Birgit
- Majewski, Jacek
- Bulman, Dennis E
- Shendure, Jay
- Graham, John M
- Boycott, Kym M
- Dobyns, William B
- Venue
- Nature Genetics
- Published
- 2012-06-24
- Volume
- 44
- Issue
- 8
- Pages
- 934-940
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3408813
- OpenAlex
- W2016910640
- Cited by
- 741
- References
- 55
- Citations by year
- 2026: 27 · 2025: 33 · 2024: 44 · 2023: 38 · 2022: 49 · 2021: 66 · 2020: 61 · 2019: 50 · 2018: 51 · 2017: 57 · 2016: 60 · 2015: 72 · 2014: 61 · 2013: 61 · 2012: 10
- FWCI
- 57.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- GRO (submittedVersion)
- Funders
- McGill University
- Cancer Research UK
- National Institutes of Health (UL1TR000124, 1rc2hl103010-01)
- Canadian Institutes of Health Research
- National Heart, Lung, and Blood Institute (RC2HL102925, RC2HL102926, RC2HL102923, UC2HL102924, RC2HL-103010, UC2HL102925, UC2HL102923, UC2HL103010, RC2HL102924, UC2HL102926)
- National Institute of General Medical Sciences (5-T32-GM08243, T32GM008243)
- National Institute of Neurological Disorders and Stroke (NS058721, R01NS046616, R01NS058721)
- National Institute of Environmental Health Sciences (HHSN273200800010C)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD36657)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- megalencephaly, PI3K/Akt signaling, AKT3, PIK3R2, PIK3CA, de novo germline mutation, postzygotic mutation, postzygotic mosaicism, overgrowth syndromes, capillary malformation, polymicrogyria, polydactyly, hydrocephalus, brain development, vascular development, limb development
- MeSH terms
- Humans, Hydrocephalus, Mutation, Syndrome, Germ-Line Mutation, Phosphatidylinositol 3-Kinases, Mutation, Missense, Proto-Oncogene Proteins c-akt, Malformations of Cortical Development, Class I Phosphatidylinositol 3-Kinases, Megalencephaly, Exome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
