Cited by 98Protein Tyrosine PhosphatasesGenetics and Neurodevelopmental DisordersProtein Kinase Regulation and GTPase Signaling

Cognitive profile of disorders associated with dysregulation of the RAS/MAPK signaling cascade

Cesarini, Laura, Alfieri, Paolo, Pantaleoni, Francesca, Vasta, Isabella, Cerutti, Marta, Petrangeli, Valentina, Mariotti, Paolo, Leoni, Chiara +6 more·2009·American Journal of Medical Genetics Part A

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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Crossref · 10.1002/ajmg.a.32488

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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].”

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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
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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