Pathogenetics of the RASopathies

William E. Tidyman, Katherine A Rauen

Research output: Contribution to journalReview article

36 Citations (Scopus)

Abstract

The RASopathies are defined as a group of medical genetics syndromes that are caused by germ-line mutations in genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) pathway. Taken together, the RASopathies represent one of the most prevalent groups of malformation syndromes affecting greater than 1 in 1,000 individuals. The Ras/MAPK pathway has been well studied in the context of cancer as it plays essential roles in growth, differentiation, cell cycle, senescence and apoptosis, all of which are also critical to normal development. The consequence of germ-line dysregulation leads to phenotypic alterations of development. RASopathies can be caused by several pathogenetic mechanisms that ultimately impact or alter the normal function and regulation of the MAPK pathway. These pathogenetic mechanisms can include functional alteration of GTPases, Ras GTPase-activating proteins, Ras guanine exchange factors, kinases, scaffolding or adaptor proteins, ubiquitin ligases, phosphatases and pathway inhibitors. Although these mechanisms are diverse, the common underlying biochemical phenotype shared by all the RASopathies is Ras/MAPK pathway activation. This results in the overlapping phenotypic features among these syndromes.

Original languageEnglish (US)
Pages (from-to)R123-R132
JournalHuman Molecular Genetics
Volume25
Issue numberR2
DOIs
StatePublished - Oct 1 2016

Fingerprint

Mitogen-Activated Protein Kinases
ras GTPase-Activating Proteins
Gene Components
Ubiquitin-Protein Ligases
Germ-Line Mutation
Cell Aging
GTP Phosphohydrolases
Medical Genetics
Guanine
Phosphoric Monoester Hydrolases
Germ Cells
Cell Cycle
Phosphotransferases
Apoptosis
Phenotype
Growth
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Pathogenetics of the RASopathies. / Tidyman, William E.; Rauen, Katherine A.

In: Human Molecular Genetics, Vol. 25, No. R2, 01.10.2016, p. R123-R132.

Research output: Contribution to journalReview article

Tidyman, William E. ; Rauen, Katherine A. / Pathogenetics of the RASopathies. In: Human Molecular Genetics. 2016 ; Vol. 25, No. R2. pp. R123-R132.
@article{24b05efd42664253bbf4d6a72d074888,
title = "Pathogenetics of the RASopathies",
abstract = "The RASopathies are defined as a group of medical genetics syndromes that are caused by germ-line mutations in genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) pathway. Taken together, the RASopathies represent one of the most prevalent groups of malformation syndromes affecting greater than 1 in 1,000 individuals. The Ras/MAPK pathway has been well studied in the context of cancer as it plays essential roles in growth, differentiation, cell cycle, senescence and apoptosis, all of which are also critical to normal development. The consequence of germ-line dysregulation leads to phenotypic alterations of development. RASopathies can be caused by several pathogenetic mechanisms that ultimately impact or alter the normal function and regulation of the MAPK pathway. These pathogenetic mechanisms can include functional alteration of GTPases, Ras GTPase-activating proteins, Ras guanine exchange factors, kinases, scaffolding or adaptor proteins, ubiquitin ligases, phosphatases and pathway inhibitors. Although these mechanisms are diverse, the common underlying biochemical phenotype shared by all the RASopathies is Ras/MAPK pathway activation. This results in the overlapping phenotypic features among these syndromes.",
author = "Tidyman, {William E.} and Rauen, {Katherine A}",
year = "2016",
month = "10",
day = "1",
doi = "10.1093/hmg/ddw191",
language = "English (US)",
volume = "25",
pages = "R123--R132",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "R2",

}

TY - JOUR

T1 - Pathogenetics of the RASopathies

AU - Tidyman, William E.

AU - Rauen, Katherine A

PY - 2016/10/1

Y1 - 2016/10/1

N2 - The RASopathies are defined as a group of medical genetics syndromes that are caused by germ-line mutations in genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) pathway. Taken together, the RASopathies represent one of the most prevalent groups of malformation syndromes affecting greater than 1 in 1,000 individuals. The Ras/MAPK pathway has been well studied in the context of cancer as it plays essential roles in growth, differentiation, cell cycle, senescence and apoptosis, all of which are also critical to normal development. The consequence of germ-line dysregulation leads to phenotypic alterations of development. RASopathies can be caused by several pathogenetic mechanisms that ultimately impact or alter the normal function and regulation of the MAPK pathway. These pathogenetic mechanisms can include functional alteration of GTPases, Ras GTPase-activating proteins, Ras guanine exchange factors, kinases, scaffolding or adaptor proteins, ubiquitin ligases, phosphatases and pathway inhibitors. Although these mechanisms are diverse, the common underlying biochemical phenotype shared by all the RASopathies is Ras/MAPK pathway activation. This results in the overlapping phenotypic features among these syndromes.

AB - The RASopathies are defined as a group of medical genetics syndromes that are caused by germ-line mutations in genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) pathway. Taken together, the RASopathies represent one of the most prevalent groups of malformation syndromes affecting greater than 1 in 1,000 individuals. The Ras/MAPK pathway has been well studied in the context of cancer as it plays essential roles in growth, differentiation, cell cycle, senescence and apoptosis, all of which are also critical to normal development. The consequence of germ-line dysregulation leads to phenotypic alterations of development. RASopathies can be caused by several pathogenetic mechanisms that ultimately impact or alter the normal function and regulation of the MAPK pathway. These pathogenetic mechanisms can include functional alteration of GTPases, Ras GTPase-activating proteins, Ras guanine exchange factors, kinases, scaffolding or adaptor proteins, ubiquitin ligases, phosphatases and pathway inhibitors. Although these mechanisms are diverse, the common underlying biochemical phenotype shared by all the RASopathies is Ras/MAPK pathway activation. This results in the overlapping phenotypic features among these syndromes.

UR - http://www.scopus.com/inward/record.url?scp=84994153762&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994153762&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddw191

DO - 10.1093/hmg/ddw191

M3 - Review article

AN - SCOPUS:84994153762

VL - 25

SP - R123-R132

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - R2

ER -