Cognitive profile of disorders associated with dysregulation of the RAS/MAPK signaling cascade
Abstract
Mutations in genes coding for transducers participating in the RAS/MAPK pathway have been identified as the molecular cause underlying a group of clinically related developmental disorders with cognitive deficits of variable severity. To determine the spectrum of cognitive defects associated with dysregulation of this signal cascade, we studied the profile of cognitive abilities in patients with mutations affecting the PTPN11, SOS1, HRAS, KRAS, BRAF, RAF1, and MEK1 genes and phenotype-genotype correlations. Our findings support the observation that heterogeneity in cognitive abilities can be at least partially ascribed to the individual affected genes and type of mutation involved. While mutations affecting transducers upstream of RAS were less frequently associated with mental retardation, mutations in downstream components of the pathway were generally associated with a more severe cognitive impairment. Among patients with a heterozygous PTPN11 mutation, the T468M substitution was associated with a mean IQ significantly higher compared to that of individuals carrying the N308D change. Our study provides insights on the range of cognitive abilities in patients with gene mutations causing dysregulation of RAS signaling suggesting that the presence and severity of cognitive involvement can be predicted in part by the gene involved.
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Disruption of the ERK/MAPK pathway can lead to a broad range of syndromes comprising craniofacial defects and cognitive deficits.
“which, when disrupted, can lead to a broad range of syndromes comprising craniofacial defects and cognitive deficits [70].”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [70]
Cites
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369 · see citing works
Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome
Tartaglia, M., Mehler, E. L., Goldberg, R. B., Zampino, G., Brunner, H. G., Kremer, H., van der Burgt, I., Crosby, A. H., Ion, A., Jeffery, S., et al. (2001) · Nature Genetics · doi:10.1038/ng772 · Cited by 1,736 · see citing works
Self-citationMAPK cascade signalling and synaptic plasticity
Thomas, G. M., & Huganir, R. L. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1346 · Cited by 1,454 · see citing works
Sweatt, J. D. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00054.x · Cited by 1,131 · see citing works
The MAPK cascade is required for mammalian associative learning
Atkins, C. M., Selcher, J. C., Petraitis, J. J., Trzaskos, J. M., & Sweatt, J. D. (1998) · Nature Neuroscience · doi:10.1038/2836 · Cited by 1,083 · see citing works
Mitogen-activated protein kinases in synaptic plasticity and memory
Sweatt, J. D. (2004) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2004.04.001 · Cited by 990 · see citing works
Tartaglia, M., Kalidas, K., Shaw, A. C., Song, X., Musat, D. L., van der Burgt, I., Brunner, H. G., Bertola, D. R., Crosby, A. H., Ion, A., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/340847 · Cited by 801 · see citing works
Self-citationGermline KRAS mutations cause Noonan syndrome
Schubbert, S., Zenker, M., Rowe, S. L., Böll, S., Klein, C., Bollag, G., van der Burgt, I., Musante, L., Kalscheuer, V., Wehner, L.-E., et al. (2006) · Nature Genetics · doi:10.1038/ng1748 · Cited by 730 · see citing works
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy
Pandit, B., Sárközy, A., Pennacchio, L. A., Carta, C., Oishi, K., Martinelli, S., Pogna, E. A., Schackwitz, W., Ustaszewska, A., Landstrom, A. P., et al. (2007) · Nature Genetics · doi:10.1038/ng2073 · Cited by 700 · see citing works
Self-citationGermline mutations in HRAS proto-oncogene cause Costello syndrome
Aoki, Y., Niihori, T., Kawame, H., Kurosawa, K., Ohashi, H., Tanaka, Y., Filocamo, M., Kato, K., Suzuki, Y., Kure, S., et al. (2005) · Nature Genetics · doi:10.1038/ng1641 · Cited by 678 · see citing works
Germline gain-of-function mutations in SOS1 cause Noonan syndrome
Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., et al. (2007) · Nature Genetics · doi:10.1038/ng1926 · Cited by 605 · see citing works
Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome
Niihori, T., Aoki, Y., Narumi, Y., Neri, G., Cavé, H., Verloès, A., Okamoto, N., Hennekam, R. C. M., Gillessen‐Kaesbach, G., Wieczorek, D., et al. (2006) · Nature Genetics · doi:10.1038/ng1749 · Cited by 597 · see citing works
Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome
Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sárközy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., et al. (2006) · Nature Genetics · doi:10.1038/ng1939 · Cited by 587 · see citing works
Self-citationGermline Mutations in Genes Within the MAPK Pathway Cause Cardio-facio-cutaneous Syndrome
Rodriguez‐Viciana, P., Tetsu, O., Tidyman, W. E., Estep, A. L., Conger, B. A., Cruz, M. S., McCormick, F. P., & Rauen, K. A. (2006) · Science · doi:10.1126/science.1124642 · Cited by 569 · see citing works
Germline gain-of-function mutations in RAF1 cause Noonan syndrome
Razzaque, A. M., Nishizawa, T., Komoike, Y., Yagi, H., Furutani, M., Amo, R., Kamisago, M., Momma, K., Katayama, H., Nakagawa, M., et al. (2007) · Nature Genetics · doi:10.1038/ng2078 · Cited by 501 · see citing works
Grouping of Multiple-Lentigines/LEOPARD and Noonan Syndromes on the PTPN11 Gene
Digilio, M. C., Conti, E., Sárközy, A., Mingarelli, R., Dottorini, T., Marino, B., Pizzuti, A., & Dallapiccola, B. (2002) · The American Journal of Human Genetics · doi:10.1086/341528 · Cited by 419 · see citing works
van der Burgt, I. (2007) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-2-4 · Cited by 365 · see citing works
NOONAN SYNDROME AND RELATED DISORDERS: Genetics and Pathogenesis
Tartaglia, M., & Gelb, B. D. (2005) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.6.080604.162305 · Cited by 355 · see citing works
Self-citationHennekam, R. C. M. (2006) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201594 · Cited by 320 · see citing works
Clinical and molecular studies in a large Dutch family with Noonan syndrome
van der Burgt, I., Berends, E., Lommen, E. J. P., van Beersum, S. E. C., Hamel, B. C. J., & Mariman, E. C. M. (1994) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320530213 · Cited by 285 · see citing works
PTPN11 mutations in LEOPARD syndrome
Legius, E., Schrander-Stumpel, C. T. R. M., Schollen, E., Pulles‐Heintzberger, C. F. M., Gewillig, M. H. M. L., & Fryns, J.-P. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.8.571 · Cited by 274 · see citing works
The cardiofaciocutaneous syndrome
Roberts, A., Allanson, J., Jadico, S. K., Kavamura, M. I., Noonan, J., Opitz, J. M., Young, T., & Neri, G. (2006) · Journal of Medical Genetics · doi:10.1136/jmg.2006.042796 · Cited by 271 · see citing works
Nava, C., Hanna, N., Michot, C., Pereira, S., Pouvreau, N., Niihori, T., Aoki, Y., Matsubara, Y., Arveiler, B., Lacombe, D., et al. (2007) · Journal of Medical Genetics · doi:10.1136/jmg.2007.050450 · Cited by 256 · see citing works
Genotype-phenotype correlations in Noonan syndrome
Zenker, M., Buheitel, G., Rauch, R., Koenig, R., Bosse, K., Kreß, W., Tietze, H. U., Doerr, H.-G., Hofbeck, M., Singer, H., et al. (2004) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2003.11.032 · Cited by 247 · see citing works
Carta, C., Pantaleoni, F., Bocchinfuso, G., Stella, L., Vasta, I., Sárközy, A., Digilio, C., Palleschi, A., Pizzuti, A., Grammatico, P., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/504394 · Cited by 225 · see citing works
Self-citationCostello syndrome: An overview
Hennekam, R. C. M. (2003) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.10019 · Cited by 214 · see citing works
Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations
Zenker, M., Lehmann, K., Schulz, A., Barth, H., Hansmann, D., Koenig, R., Korinthenberg, R., Kreiß‐Nachtsheim, M., Meinecke, P., Morlot, S., et al. (2006) · Journal of Medical Genetics · doi:10.1136/jmg.2006.046300 · Cited by 202 · see citing works
Voron, D. A., Hatfield, H. H., & Kalkhoff, R. K. (1976) · The American Journal of Medicine · doi:10.1016/0002-9343(76)90764-6 · Cited by 198 · see citing works
Gelb, B. D., & Tartaglia, M. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl197 · Cited by 197 · see citing works
Self-citationStops along the RAS pathway in human genetic disease
Bentires-Alj, M., Kontaridis, M. I., & Neel, B. G. (2006) · Nature Medicine · doi:10.1038/nm0306-283 · Cited by 190 · see citing works
Ras-related and MAPK signalling in neuronal plasticity and memory formation
Mazzucchelli, C., & Brambilla, R. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000722 · Cited by 164 · see citing works
A Role for ERK MAP Kinase in Physiologic Temporal Integration in Hippocampal Area CA1Preprint
Selcher, J. C., Weeber, E. J., Christian, J., Nekrasova, T., Landreth, G. E., & Sweatt, J. D. (2003) · Learning & Memory · doi:10.1101/lm.51103 · Cited by 155 · see citing works
Cognitive Profile of Neurofibromatosis Type 1
Levine, T. M., Materek, A., Abel, J., O’Donnell, M., & Cutting, L. E. (2006) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2006.01.006 · Cited by 150 · see citing works
Coffin-Lowry syndrome: clinical and molecular features
Hanauer, A., & Young, I. D. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.10.705 · Cited by 149 · see citing works
Molecular Neurobiology of Human Cognition
Weeber, E. J., & Sweatt, J. D. (2002) · Neuron · doi:10.1016/s0896-6273(02)00634-7 · Cited by 145 · see citing works
Zenker, M., Horn, D., Wieczorek, D., Allanson, J. E., Pauli, S., van der Burgt, I., Doerr, H. G., Gaspar, H., Hofbeck, M., Gillessen‐Kaesbach, G., et al. (2007) · Journal of Medical Genetics · doi:10.1136/jmg.2007.051276 · Cited by 138 · see citing works
Zampino, G., Pantaleoni, F., Carta, C., Cobellis, G., Vasta, I., Neri, C., Pogna, E. A., Feo, E. D., Delogu, A. B., Sárközy, A., et al. (2006) · Human Mutation · doi:10.1002/humu.20431 · Cited by 132 · see citing works
Self-citationNeurological complications of cardio‐facio‐cutaneous syndrome
Yoon, G., Rosenberg, J., Blasér, S., & Rauen, K. A. (2007) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2007.00894.x · Cited by 128 · see citing works
Recent developments in neurofibromatosis type 1
Lee, M., & Stephenson, D. A. (2007) · Current Opinion in Neurology · doi:10.1097/wco.0b013e3280895da8 · Cited by 120 · see citing works
Deregulated Ras signaling in developmental disorders: new tricks for an old dog
Schubbert, S., Bollag, G. E., & Shannon, K. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2006.12.004 · Cited by 116 · see citing works
The Griffiths Mental Development Scales from birth to 2 years
Griffiths, R. R. (1996) · Medical Entomology and Zoology · Cited by 114 · see citing works
HRAS and the Costello syndrome
Rauen, K. (2007) · Clinical Genetics · doi:10.1111/j.1399-0004.2007.00743.x · Cited by 111 · see citing works
Mutation and phenotypic spectrum in patients with cardio‐facio‐cutaneous and Costello syndrome
Schulz, A., Albrecht, B., Arıcı, C., van der Burgt, I., Buske, A., Gillessen‐Kaesbach, G., Heller, R., Horn, D., Hübner, C., Korenke, G. C., et al. (2007) · Clinical Genetics · doi:10.1111/j.1399-0004.2007.00931.x · Cited by 109 · see citing works
Narumi, Y., Aoki, Y., Niihori, T., Neri, G., Cavé, H., Verloès, A., Nava, C., Kavamura, M. I., Okamoto, N., Kurosawa, K., et al. (2007) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31658 · Cited by 106 · see citing works
Aberrant early-phase ERK inactivation impedes neuronal function in fragile X syndrome
Kim, S. H., Markham, J. A., Weiler, I. J., & Greenough, W. T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800257105 · Cited by 97 · see citing works
Gripp, K. W., Lin, A. E., Nicholson, L., Allen, W., Cramer, A. E., Jones, K. L., Kutz, W. E., Peck, D. S., Rebolledo, M. A., Wheeler, P. G., et al. (2007) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31815 · Cited by 95 · see citing works
Psychological profile of children with Noonan syndrome
Lee, D. A., Portnoy, S., Hill, P., Gillberg, C., & Patton, M. (2005) · Developmental Medicine & Child Neurology · doi:10.1017/s001216220500006x · Cited by 92 · see citing works
Psychological profile of children with Noonan syndrome
Lee, D. A., Portnoy, S., Hill, P., Gillberg, C., & Patton, M. A. (2007) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2005.tb01037.x · Cited by 74 · see citing works
Noonan syndrome: Psychological and psychiatric aspects
Verhoeven, W. M. A., Wingbermühle, E., Egger, J. I. M., van der Burgt, I., & Tuinier, S. (2007) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32115 · Cited by 64 · see citing works
Costello syndrome and neurological abnormalities
Delrue, M., Chateil, J., Arveiler, B., & Lacombe, D. (2003) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.20330 · Cited by 61 · see citing works
An unexpected new role of mutant Ras: perturbation of human embryonic development
Kratz, C. P., Niemeyer, C. M., & Zenker, M. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-006-0135-4 · Cited by 57 · see citing works
Longitudinal assessment of cognitive characteristics in Costello syndrome
Axelrad, M. E., Nicholson, L., Stabley, D. L., Sol‐Church, K., & Gripp, K. W. (2007) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31968 · Cited by 44 · see citing works
Extracellular Signal-Regulated Kinases Regulate Dendritic Growth in Rat Sympathetic Neurons
Kim, I. J., Drahushuk, K. M., Kim, W.-Y., Gonsiorek, E. A., Lein, P. J., Andres, D., & Higgins, D. M. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3286-03.2004 · Cited by 40 · see citing works
Sweatt, J. D., & Weeber, E. J. (2003) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000046875.56865.cc · Cited by 28 · see citing works
Sweatt, J. D., Weeber, E. J., & Lombroso, P. J. (2003) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000046859.56865.a8 · Cited by 11 · see citing works
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Roberts, A. E., Allanson, J. E., Tartaglia, M., & Gelb, B. D. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61023-x · Cited by 791 · see citing works
Self-citationNoonan Syndrome: Clinical Features, Diagnosis, and Management Guidelines
Romano, A. A., Allanson, J. E., Dahlgren, J., Gelb, B. D., Hall, B. D., Pierpont, M. E., Roberts, A. E., Robinson, W., Takemoto, C. M., & Noonan, J. A. (2010) · PEDIATRICS · doi:10.1542/peds.2009-3207 · Cited by 628 · see citing works
Noonan syndrome and clinically related disorders
Tartaglia, M., Gelb, B. D., & Zenker, M. (2011) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.09.002 · Cited by 420 · see citing works
Self-citationNoonan Syndrome: Clinical Aspects and Molecular Pathogenesis
Tartaglia, M., Zampino, G., & Gelb, B. D. (2010) · Molecular Syndromology · doi:10.1159/000276766 · Cited by 251 · see citing works
Self-citationThe RASopathy Family: Consequences of Germline Activation of the RAS/MAPK Pathway
Tajan, M., Paccoud, R., Branka, S., Édouard, T., & Yart, A. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00232 · Cited by 240 · see citing works
Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines
Pierpont, M. E., Magoulas, P. L., Adi, S., Kavamura, M. I., Neri, G., Noonan, J. A., Pierpont, E. I., Reinker, K. A., Roberts, A. E., Shankar, S. P., et al. (2014) · PEDIATRICS · doi:10.1542/peds.2013-3189 · Cited by 211 · see citing works
Tartaglia, M., & Gelb, B. D. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05790.x · Cited by 198 · see citing works
Self-citationSelf-domestication in Homo sapiens: Insights from comparative genomics
Theofanopoulou, C., Gastaldon, S., O’Rourke, T., Samuels, B. D., Messner, A., Martins, P. T., Delogu, F., Alamri, S., & Boeckx, C. (2017) · PLOS ONE · doi:10.1371/journal.pone.0185306 · Cited by 174 · see citing works
Mechanism and treatment for learning and memory deficits in mouse models of Noonan syndrome
Lee, Y., Ehninger, D., Zhou, M., Oh, J.-Y., Kang, M., Kwak, C., Ryu, H.-H., Butz, D. H., Araki, T., Cai, Y., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3863 · Cited by 150 · see citing works
Costello syndrome: Clinical phenotype, genotype, and management guidelines
Gripp, K. W., Morse, L. A., Axelrad, M. E., Chatfield, K. C., Chidekel, A. S., Dobyns, W. B., Doyle, D., Kerr, B. A., Lin, A. E., Schwartz, D. D., et al. (2019) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.61270 · Cited by 134 · see citing works
Wong, H., & Hoeffer, C. A. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.04.010 · Cited by 128 · see citing works
Neurodevelopmental disorders in children with neurofibromatosis type 1
Vogel, A. C., Gutmann, D. H., & Morris, S. M. (2017) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.13526 · Cited by 95 · see citing works
RASopathies: Clinical Diagnosis in the First Year of Life
Digilio, M. C., Lepri, F. R., Baban, A., Dentici, M. L., Versacci, P., Capolino, R., Ferese, R., Luca, A. D., Tartaglia, M., Marino, B., et al. (2010) · Molecular Syndromology · doi:10.1159/000331266 · Cited by 96 · see citing works
Self-citationBehavioral Profile in RASopathies
Alfieri, P., Piccini, G., Caciolo, C., Perrino, F., Gambardella, M. L., Mallardi, M., Cesarini, L., Leoni, C., Leone, D., FOSSATI, C., et al. (2014) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36374 · Cited by 83 · see citing works
Self-citationThe Ras Superfamily of Small GTPases in Non-neoplastic Cerebral Diseases
Qu, L., Pan, C., He, S., Lang, B., Gao, G.-D., Wang, X., & Wang, Y. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00121 · Cited by 77 · see citing works
Pierpont, E. I., Tworog‐Dube, E., & Roberts, A. E. (2014) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.12621 · Cited by 68 · see citing works
Neurodevelopmental Aspects of RASopathies
Kim, Y. E., & Baek, S. T. (2019) · Molecules and Cells · doi:10.14348/molcells.2019.0037 · Cited by 68 · see citing works
Pierpont, E. I., Pierpont, M. E., Mendelsohn, N. J., Roberts, A. E., Tworog‐Dube, E., Rauen, K. A., & Seidenberg, M. S. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33268 · Cited by 56 · see citing works
Novel BRAF mutation in a patient with LEOPARD syndrome and normal intelligence
Koudová, M., Seemanová, E., & Zenker, M. (2009) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2009.04.006 · Cited by 55 · see citing works
The impact of RASopathy-associated mutations on CNS development in mice and humans
Kang, M., & Lee, Y.-S. (2019) · Molecular Brain · doi:10.1186/s13041-019-0517-5 · Cited by 40 · see citing works
Pierpont, E. I. (2015) · Journal of Pediatric Neuropsychology · doi:10.1007/s40817-015-0005-5 · Cited by 46 · see citing works
CHD associated with syndromic diagnoses: peri-operative risk factors and early outcomes
Landis, B. J., Cooper, D. S., & Hinton, R. B. (2015) · Cardiology in the Young · doi:10.1017/s1047951115001389 · Cited by 43 · see citing works
Psychopathological features in Noonan syndrome
Perrino, F., Licchelli, S., Serra, G., Piccini, G., Caciolo, C., Pasqualetti, P., Cirillo, F., Leoni, C., Digilio, M. C., Zampino, G., et al. (2017) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2017.09.009 · Cited by 41 · see citing works
Self-citationPierpont, E. I., Kenney‐Jung, D. L., Shanley, R., Zatkalik, A. L., Whitmarsh, A. E., Kroening, S. J., Roberts, A. E., & Zenker, M. (2022) · Genetics in Medicine · doi:10.1016/j.gim.2022.04.004 · Cited by 41 · see citing works
Neurocognitive, adaptive, and behavioral functioning of individuals with Costello syndrome: A review
Axelrad, M. E., Schwartz, D. D., Katzenstein, J. M., Hopkins, E., & Gripp, K. W. (2011) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30299 · Cited by 41 · see citing works
Longitudinal course of cognitive, adaptive, and behavioral characteristics in Costello syndrome
Axelrad, M. E., Schwartz, D. D., Fehlis, J. E., Hopkins, E., Stabley, D. L., Sol‐Church, K., & Gripp, K. W. (2009) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33126 · Cited by 38 · see citing works
Holter, M. C., Hewitt, L. T., Koebele, S. V., Judd, J. M., Xing, L., Bimonte‐Nelson, H. A., Conrad, C. D., Araki, T., Neel, B. G., Snider, W. D., et al. (2019) · PLoS Genetics · doi:10.1371/journal.pgen.1008108 · Cited by 38 · see citing works
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Carcavilla, A., Suárez-Ortega, L., Sánchez, A. R., Casado, I. G., Ramon‐Krauel, M., Labarta, J. I., González, S. Q., Galán, I. R., Zubicaray, B. E., & López‐Siguero, J. P. (2020) · Anales de Pediatría · doi:10.1016/j.anpedi.2020.04.008 · Cited by 35 · see citing works
Learning and memory in children with Noonan syndrome
Pierpont, E. I., Tworog‐Dube, E., & Roberts, A. E. (2013) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36075 · Cited by 35 · see citing works
Leoni, C., Triumbari, E. K. A., Vollono, C., Onesimo, R., Podagrosi, M., Giorgio, V., Kuczynska, E. M., Veltri, S., Tartaglia, M., & Zampino, G. (2019) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.61111 · Cited by 33 · see citing works
Self-citationEnhanced human brain associative plasticity in Costello syndrome
Dileone, M., Profice, P., Pilato, F., Alfieri, P., Cesarini, L., Mercuri, E. M., Leoni, C., Tartaglia, M., Iorio, R. D., Zampino, G., et al. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.191072 · Cited by 32 · see citing works
Self-citationCognitive functioning of adults with Noonan syndrome: a case–control study
Wingbermühle, E., Roelofs, R. L., van der Burgt, I., Souren, P. M., Verhoeven, W. M. A., Kessels, R. P. C., & Egger, J. I. M. (2012) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2012.00821.x · Cited by 31 · see citing works
Yeh, E., Dao, D. Q., Wu, Z. Y., Kandalam, S., Camacho, F. M., Tom, C., Zhang, W., Krencik, R., Rauen, K. A., Ullian, E. M., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.238 · Cited by 31 · see citing works
Alfieri, P., Cesarini, L., Mallardi, M., Piccini, G., Caciolo, C., Leoni, C., Mirante, N., Pantaleoni, F., Digilio, M. C., Gambardella, M. L., et al. (2011) · Behavior Genetics · doi:10.1007/s10519-011-9446-5 · Cited by 29 · see citing works
Self-citationNoonan syndrome: genetic and clinical update and treatment options
Carcavilla, A., Suárez-Ortega, L., Sánchez, A. R., Casado, I. G., Ramon‐Krauel, M., Labarta, J. I., González, S. Q., Galán, I. R., & López‐Siguero, J. P. (2020) · Anales de Pediatría (English Edition) · doi:10.1016/j.anpede.2020.04.009 · Cited by 28 · see citing works
Wingbermühle, E., Roelofs, R. L., Oomens, W., Kramer, J., Draaisma, J. M. T., Leenders, E. K. S. M., Kleefstra, T., Kessels, R. P. C., & Egger, J. I. M. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11164735 · Cited by 28 · see citing works
Papadopoulou, E., Sifakis, S., Sol‐Church, K., Klein‐Zighelboim, E., Stabley, D. L., Raissaki, M., Gripp, K. W., & Kalmanti, M. (2011) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33787 · Cited by 27 · see citing works
Function and disability in children with Costello syndrome and Cardiofaciocutaneous syndrome
Johnson, B. A., Goldberg‐Strassler, D., Gripp, K. W., Thacker, M. M., Leoni, C., & Stevenson, D. A. (2014) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36828 · Cited by 24 · see citing works
Self-citationPierpont, E. I., & Wolford, M. (2016) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37725 · Cited by 24 · see citing works
Tafazoli, A., Eshraghi, P., Pantaleoni, F., Vakili, R., Moghaddassian, M., Ghahraman, M., Muto, V., Paolacci, S., Golyan, F. F., & Abbaszadegan, M. R. (2017) · Advances in Medical Sciences · doi:10.1016/j.advms.2017.07.001 · Cited by 24 · see citing works
Self-citationSynaptic Function and Dysfunction in Lysosomal Storage Diseases
Rebiai, R., Givogri, M. I., Gowrishankar, S., Cologna, S. M., Alford, S. T., & Bongarzone, E. R. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.619777 · Cited by 21 · see citing works
Pragmatic language impairment in children with Noonan syndrome
Selås, M., & Helland, W. A. (2016) · Clinical Linguistics & Phonetics · doi:10.1080/02699206.2016.1188422 · Cited by 21 · see citing works
Understanding intellectual disability through RASopathies
Martín, A. S., & Pagani, M. R. (2014) · Journal of Physiology-Paris · doi:10.1016/j.jphysparis.2014.05.003 · Cited by 19 · see citing works
Neuroactive effects of cotinine on the hippocampus: Behavioral and biochemical parameters
Aguiar, R. B., Parfitt, G. M., Jaboinski, J., & Barros, D. M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.03.032 · Cited by 20 · see citing works
Yan, X., Zhang, B., Lu, W., Peng, L., Yang, Q., Cao, W., Lin, S., Yu, W., Li, X., Ke, Y., et al. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0222-7 · Cited by 17 · see citing works
Social behavior in RASopathies and idiopathic autism
Foy, A. M. H., Hudock, R. L., Shanley, R., & Pierpont, E. I. (2022) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-021-09414-w · Cited by 16 · see citing works
Visual processing in Noonan syndrome: Dorsal and ventral stream sensitivity
Alfieri, P., Cesarini, L., Rose, P. D., Ricci, D., Selicorni, A., Menghini, D., Guzzetta, A., Baranello, G., Tinelli, F., Mallardi, M., et al. (2011) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.34229 · Cited by 16 · see citing works
Self-citationMcIntosh, S., Howell, L. L., & Hemby, S. E. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00088 · Cited by 14 · see citing works
RASopathies are associated with a distinct personality profile
Bizaoui, V., Gage, J., Brar, R., Rauen, K. A., & Weiss, L. A. (2018) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32632 · Cited by 15 · see citing works
Jurcă, M. C., Iuhas, O. A., Puiu, M., Chiriță-Emandi, A., Andreescu, N. I., Petcheși, C. D., Jurcă, A. D., Magyar, I., Jurca, S., Kozma, K., et al. (2022) · Romanian Journal of Morphology and Embryology · doi:10.47162/rjme.62.2.23 · Cited by 13 · see citing works
Koh, A. L., Tan, E. S., Brett, M., Lai, A., Jamuar, S. S., Ng, I., & Tan, E. (2019) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.581 · Cited by 12 · see citing works
Kang, M., Choi, J., Han, J. H., Araki, T., Kim, S.-W., Ryu, H.-H., Kim, M.-G., Kim, S., Jang, H.-B., Kim, S. Y., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci176631 · Cited by 11 · see citing works
Manic and Depressive Symptoms in Children Diagnosed with Noonan Syndrome
Alfieri, P., Cumbo, F., Serra, G., Trasolini, M., Frattini, C., Scibelli, F., Licchelli, S., Cirillo, F., Caciolo, C., Casini, M. P., et al. (2021) · Brain Sciences · doi:10.3390/brainsci11020233 · Cited by 10 · see citing works
Self-citationThe RASopathies: Biology, genetics and therapeutic options
Longo, J. F., & Carroll, S. L. (2022) · Advances in cancer research · doi:10.1016/bs.acr.2021.07.007 · Cited by 10 · see citing works
Leoni, C., Giorgio, V., Stella, G., Onesimo, R., Triumbari, E. K. A., Podagrosi, M., Kuczynska, E. M., Vollono, C., Lindley, K. J., & Zampino, G. (2022) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.62917 · Cited by 10 · see citing works
Self-citationDavico, C., Borgogno, M., Campagna, F., D’Alessandro, R., Ricci, F., Amianto, F., Mussa, A., Carli, D., Ferrero, G. B., & Vitiello, B. (2021) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0000000000000991 · Cited by 9 · see citing works
Phenotypic and Genetic Characteristics of Five Korean Patients with Costello Syndrome
Choi, N., Ko, J. M., Shin, S. H., Kim, E., Kim, H., Song, M. K., & Choi, C. W. (2019) · Cytogenetic and Genome Research · doi:10.1159/000502045 · Cited by 8 · see citing works
Acute encephalopathy with combination dabrafenib/trametinib therapy
Cooper, J., Kodali, D., & Higa, G. M. (2016) · Journal of Oncology Pharmacy Practice · doi:10.1177/1078155216638551 · Cited by 8 · see citing works
Behavioral phenotype in Costello syndrome with atypical mutation: A case report
Alfieri, P., Caciolo, C., Piccini, G., D’Elia, L., Valeri, G., Menghini, D., Tartaglia, M., Digilio, M. C., Dallapiccola, B., & Vicari, S. (2014) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32279 · Cited by 7 · see citing works
Self-citationMontanaro, F. A. M., Alfieri, P., Caciolo, C., Cumbo, F., Piga, S., Tartaglia, M., Licchelli, S., Digilio, M. C., & Vicari, S. (2022) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.32025 · Cited by 7 · see citing works
Self-citationBraun-Walicka, N., Pluta, A., Wolak, T. P., Maj, E., Maryniak, A., Goś, M., Abramowicz, A., Landowska, A., Obersztyn, E., & Bal, J. (2023) · Genes · doi:10.3390/genes14122173 · Cited by 6 · see citing works
Sivasankaran, A., Padmalatha, V. O., Saranya, G., Durgadatta, T., Raseswari, T., Kulashekaran, K. M., Meena, J., Chandra, N., Lalji, S., & Kandukuri, L. R. (2011) · Molecular Cytogenetics · doi:10.1186/1755-8166-4-21 · Cited by 6 · see citing works
Epilepsy in cardiofaciocutaneous syndrome: Clinical burden and response to anti‐seizure medication
Kenney‐Jung, D. L., Collazo-Lopez, J. E., Rogers, D. J., Shanley, R., Zatkalik, A. L., Whitmarsh, A. E., Roberts, A. E., Zenker, M., & Pierpont, E. I. (2023) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.63428 · Cited by 5 · see citing works
Shoc2/Sur8 Protein Regulates Neurite Outgrowth
León‐Espinosa, G., Sánchez‐Ruiloba, L., Pérez-Rodríguez, A., Gragera, T., Martinez, N. J., Hernandez, S. F., Anta, B., Calero, O., García-Domínguez, C. A., Dura, L. M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114837 · Cited by 5 · see citing works
Chavarría‐Siles, I., Rijpkema, M., Lips, E. H., Vásquez, A. A., Verhage, M., Franke, B., Fernández, G., & Danielle Posthuma, B. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhs061 · Cited by 5 · see citing works
Aberrant Cortical Layer Development of Brain Organoids Derived from Noonan Syndrome-iPSCs
Kim, B., Koh, Y., Do, H., Ju, Y., Choi, J. B., Cho, G., Yoo, H., Lee, B. H., Han, J., Park, J.-E., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213861 · Cited by 7 · see citing works
Language profiles in Noonan Syndrome – A multiple case study
Selås, M. (2024) · Clinical Linguistics & Phonetics · doi:10.1080/02699206.2023.2298976 · Cited by 4 · see citing works
Recognition Memory in Noonan Syndrome
Costanzo, F., Alfieri, P., Caciolo, C., Bergonzini, P., Perrino, F., Zampino, G., Leoni, C., Menghini, D., Digilio, M. C., Tartaglia, M., et al. (2021) · Brain Sciences · doi:10.3390/brainsci11020169 · Cited by 4 · see citing works
Self-citationMolecular Determinants of Neurocognitive Deficits in Glioma: Based on 2021 WHO Classification
Zhang, K., Yang, T., Xia, Y., Guo, X., Chen, W., Wang, L., Li, J., Wu, J., Xiao, Z., Zhang, X., et al. (2024) · Journal of Molecular Neuroscience · doi:10.1007/s12031-023-02173-4 · Cited by 3 · see citing works
Developmental effect of RASopathy mutations on neuronal network activity on a chip
Weiss, E., Guhathakurta, D., Petrušková, A., Hundrup, V., Zenker, M., & Fejtová, A. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1388409 · Cited by 3 · see citing works
ERKquake in Noonan syndrome: one step closer to personalized medicine
Costa‐Mattioli, M. (2014) · Nature Neuroscience · doi:10.1038/nn.3879 · Cited by 3 · see citing works
Domain-specific phenotypic profiles in RAF1-related Noonan syndrome
Gazzin, A., Calvo, M., Rondot, F., Reynolds, G. J., Leoni, C., Niceta, M., Dentici, M. L., Digilio, M. C., Lepri, F. R., Monda, E., et al. (2026) · European Journal of Human Genetics · doi:10.1038/s41431-025-02002-9 · Cited by 2 · see citing works
Self-citationNoonan syndrome with somnambulism: A rare case report
Sahu, S., Chaudhury, S., & Saldanha, D. (2020) · Industrial Psychiatry Journal · doi:10.4103/ipj.ipj_84_19 · Cited by 2 · see citing works
Rogers, D. J., Hudock, R. L., Dimian, A. F., Collazo-Lopez, J. E., Shanley, R., & Pierpont, E. I. (2025) · Journal of Intellectual Disability Research · doi:10.1111/jir.13247 · Cited by 2 · see citing works
Developmental and Neurological Features of Noonan Syndrome
Totoiu, M. O. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815348-2.00006-2 · Cited by 2 · see citing works
Yıldırım, R., Ünal, E., Özalkak, Ş., Akalın, A., Aykut, A., & Yılmaz, N. (2023) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.galenos.2023.2023-5-16 · Cited by 1 · see citing works
Cognitive Development and Learning in RASopathies
McNeill, A. M., Rogers, D. J., & Pierpont, E. I. (2024) · Springer eBooks · doi:10.1007/978-3-031-62945-7_26 · Cited by 1 · see citing works
Moriya, A., Inoue, S.-I., Saitow, F., Keitoku, M., Suzuki, N., Oike, E., Urano, E., Matsumoto, E., Suzuki, H., Aoki, Y., et al. (2025) · Human Molecular Genetics · doi:10.1093/hmg/ddae196 · Cited by 1 · see citing works
Molecular and Cellular Approaches to Cognitive Impairments Associated with NF1 and Other Rasopathies
Lee, Y., & Silva, A. J. (2012) · Springer eBooks · doi:10.1007/978-3-642-32864-0_37 · Cited by 1 · see citing works
Noonan syndrome in 12-year-old male: Case report and orthodontic management of the occlusion
Chatzistavrou, E., & Georgios, A. (2020) · Balkan Journal of Dental Medicine · doi:10.2478/bjdm-2020-0020 · Cited by 1 · see citing works
Pre-exposure cognitive performance variability is associated with severity of respiratory infection
Zhai, Y., Doraiswamy, P. M., Woods, C. W., Turner, R. B., Burke, T. W., Ginsburg, G. S., & Hero, A. O. (2022) · Scientific Reports · doi:10.1038/s41598-022-26081-6 · Cited by 1 · see citing works
Specific Functions of ERK/MAPK Signaling in Brain Development and Neurocognition
Holter, M. C. (2019) · Cited by 1 · see citing works
Genetics of Cognition-What can Developmental Disorders Teach Us?
Kerner, B. (2010) · InTech eBooks · doi:10.5772/7122
Neuropsychologische kenmerken van het noonansyndroom1
Wingbermühle, P. A. M., Egger, J. I. M., Verhoeven, W. M. A., & van der Burgt, I. (2012) · Neuropraxis · doi:10.1007/s12474-012-0008-2
The Molecular Pathogenesis of Noonan Syndrome-Associated RAF1 Mutations
Wu, X. (2014) · TSpace (University of Toronto)
Síndrome cardio-facio-cutáneo: reporte de caso
Acosta-Aragón, M. A., Sotelo-Muñoz, N. F., Gutiérrez-Montufar, O. O., Chicué-Ossa, D. M., & Ordóñez-Bastidas, M. S. (2016) · Medicina y Laboratorio · doi:10.36384/01232576.96
Noonan and Ras/MAPK Pathway Syndromes
Noonan, J. A. (2021) · Springer eBooks · doi:10.1007/978-3-319-91280-6_355
Noonan and Ras/Mapk Pathway Syndromes
Noonan, J. A. (2017) · Springer eBooks · doi:10.1007/978-1-4614-6435-8_355-5
Noonan and Ras/Mapk Pathway Syndromes
Noonan, J. A. (2012) · Springer eBooks · doi:10.1007/978-1-4419-1698-3_355
Noonan syndrome with Phenotype of hypertrophic Cardiomyopathy: Clinical Observation
Михайловна, К. С., Ринейская, Н. М., Chakova, N. N., Ниязова, С. С., Севрук, Т. А., & Гайдель, И. К. (2020) · Кардиология в Беларуси · doi:10.34883/pi.2020.12.1.011
Autism and Social Behavior in RASopathies
Foy, A. M. H., Hudock, R. L., & Pierpont, E. I. (2024) · Springer eBooks · doi:10.1007/978-3-031-62945-7_28
McGhee, C., Plank, J. R., Pannone, L., Russo, O., Fuhrmann, N., Ruggeri, A., Radio, F. C., Martinelli, S., Tartaglia, M., & Green, T. (2025) · Molecular Autism · doi:10.1186/s13229-025-00681-1
Self-citationKim, G. J., Malaquias, A. C., Bertola, D. R., Rezende, R. C., Cellin, L. D. P., Pires, L. V. L., Santillan‐Vasconez, A. M., Lerário, A. M., Scalco, R. C., & Jorge, A. A. L. (2025) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.64291
Evaluación on-line de la competencia narrativa en el síndrome de Noonan
Pérez-Sanjurjo, T., Martínez, V., & Itza, E. D. (2026) · Revista de Logopedia Foniatría y Audiología · doi:10.1016/j.rlfa.2025.100549
Etude des anomalies du métabolisme énergétique associées au syndrome de Noonan
Branka, S. (2019) · theses.fr (ABES) · doi:10.70675/b0d081a3z3492z4457za237zcabd6ccc0a76
森谷, 晃. (2026) · Nihon Ika Daigaku Igakkai Zasshi · doi:10.1272/manms.22.233
Clinical, genetic and functional characterization of intellectual disability disorders
Zweier, C. (2014) · Radboud Repository (Radboud University)
- Authors
- Cesarini, L., Alfieri, P., Pantaleoni, F., Vasta, I., Cerutti, M., Petrangeli, V., Mariotti, P., Leoni, C., Ricci, D., Vicari, S., Selicorni, A., Tartaglia, M., Mercuri, E., & Zampino, G.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- Istituto Superiore di Sanità (IT)
- Bambino Gesù Children's Hospital (IT)
- Corresponding author
- Mercuri, Eugenio
- ORCID
- Venue
- American Journal of Medical Genetics Part A
- Publisher
- Wiley
- Published
- 2009-01-09
- Volume
- 149A
- Issue
- 2
- Pages
- 140-146
- ISSN
- 1552-4825 (ISSN-L)
- 1552-4833
- OpenAlex
- W2003312419
- Cited by
- 98
- References
- 55
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 9 · 2021: 6 · 2020: 5 · 2019: 11 · 2018: 2 · 2017: 7 · 2016: 5 · 2015: 2 · 2014: 11 · 2013: 4 · 2012: 5
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Medical Genetics Part A (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- RAS/MAPK pathway, cognitive impairment, intellectual disability, PTPN11, SOS1, HRAS, KRAS, BRAF, Raf-1, MEK1, genotype-phenotype correlation, mutation severity, IQ, developmental disorders
- MeSH terms
- Adolescent, Adult, Child, Developmental Disabilities, Child, Preschool, Cognition Disorders, Female, Humans, Infant, Male, Mutation, Phenotype, Proto-Oncogene Proteins p21(ras), ras Proteins, Proto-Oncogene Proteins c-raf, SOS1 Protein, MAP Kinase Signaling System, MAP Kinase Kinase 1, Proto-Oncogene Proteins B-raf, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Young Adult
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