RASopathies: The musculoskeletal consequences and their etiology and pathogenesis

John L. Fowlkes; Kathryn M. Thrailkill; R. Clay Bunn

doi:10.1016/j.bone.2021.116060

RASopathies: The musculoskeletal consequences and their etiology and pathogenesis

John L. Fowlkes, Kathryn M. Thrailkill, R. Clay Bunn

Research output: Contribution to journal › Review article › peer-review

6 Scopus citations

Abstract

The RASopathies comprise an ever-growing number of clinical syndromes resulting from germline mutations in components of the RAS/MAPK signaling pathway. While multiple organs and tissues may be affected by these mutations, this review will focus on how these mutations specifically impact the musculoskeletal system. Herein, we review the genetics and musculoskeletal phenotypes of these syndromes in humans. We discuss how mutations in the RASopathy syndromes have been studied in translational mouse models. Finally, we discuss how signaling molecules within the RAS/MAPK pathway are involved in normal and abnormal bone biology in the context of osteoblasts, osteoclasts and chondrocytes.

Original language	English
Article number	116060
Journal	Bone
Volume	152
DOIs	https://doi.org/10.1016/j.bone.2021.116060
State	Published - Nov 2021

Bibliographical note

Funding Information:
This work was supported by a grant from the National Institutes of Health to J.L.F. ( R56DK084045 ). Additional funding was provided by the University of Kentucky Barnstable Brown Diabetes Center.

Publisher Copyright:
© 2021 Elsevier Inc.

Keywords

Capillary malformation-arteriovenous malformation syndrome
Cardio-facio-cutaneous syndrome
Costello syndrome
Legius syndrome
Neurofibromatosis type 1
Noonan syndrome
RAS/MAPK pathway

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Histology
Physiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bone.2021.116060

Cite this

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title = "RASopathies: The musculoskeletal consequences and their etiology and pathogenesis",

abstract = "The RASopathies comprise an ever-growing number of clinical syndromes resulting from germline mutations in components of the RAS/MAPK signaling pathway. While multiple organs and tissues may be affected by these mutations, this review will focus on how these mutations specifically impact the musculoskeletal system. Herein, we review the genetics and musculoskeletal phenotypes of these syndromes in humans. We discuss how mutations in the RASopathy syndromes have been studied in translational mouse models. Finally, we discuss how signaling molecules within the RAS/MAPK pathway are involved in normal and abnormal bone biology in the context of osteoblasts, osteoclasts and chondrocytes.",

keywords = "Capillary malformation-arteriovenous malformation syndrome, Cardio-facio-cutaneous syndrome, Costello syndrome, Legius syndrome, Neurofibromatosis type 1, Noonan syndrome, RAS/MAPK pathway",

author = "Fowlkes, {John L.} and Thrailkill, {Kathryn M.} and Bunn, {R. Clay}",

note = "Funding Information: This work was supported by a grant from the National Institutes of Health to J.L.F. ( R56DK084045 ). Additional funding was provided by the University of Kentucky Barnstable Brown Diabetes Center. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = nov,

doi = "10.1016/j.bone.2021.116060",

language = "English",

volume = "152",

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T2 - The musculoskeletal consequences and their etiology and pathogenesis

AU - Fowlkes, John L.

AU - Thrailkill, Kathryn M.

AU - Bunn, R. Clay

N1 - Funding Information: This work was supported by a grant from the National Institutes of Health to J.L.F. ( R56DK084045 ). Additional funding was provided by the University of Kentucky Barnstable Brown Diabetes Center. Publisher Copyright: © 2021 Elsevier Inc.

PY - 2021/11

Y1 - 2021/11

N2 - The RASopathies comprise an ever-growing number of clinical syndromes resulting from germline mutations in components of the RAS/MAPK signaling pathway. While multiple organs and tissues may be affected by these mutations, this review will focus on how these mutations specifically impact the musculoskeletal system. Herein, we review the genetics and musculoskeletal phenotypes of these syndromes in humans. We discuss how mutations in the RASopathy syndromes have been studied in translational mouse models. Finally, we discuss how signaling molecules within the RAS/MAPK pathway are involved in normal and abnormal bone biology in the context of osteoblasts, osteoclasts and chondrocytes.

AB - The RASopathies comprise an ever-growing number of clinical syndromes resulting from germline mutations in components of the RAS/MAPK signaling pathway. While multiple organs and tissues may be affected by these mutations, this review will focus on how these mutations specifically impact the musculoskeletal system. Herein, we review the genetics and musculoskeletal phenotypes of these syndromes in humans. We discuss how mutations in the RASopathy syndromes have been studied in translational mouse models. Finally, we discuss how signaling molecules within the RAS/MAPK pathway are involved in normal and abnormal bone biology in the context of osteoblasts, osteoclasts and chondrocytes.

KW - Capillary malformation-arteriovenous malformation syndrome

KW - Cardio-facio-cutaneous syndrome

KW - Costello syndrome

KW - Legius syndrome

KW - Neurofibromatosis type 1

KW - Noonan syndrome

KW - RAS/MAPK pathway

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AN - SCOPUS:85110351262

VL - 152

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ER -

RASopathies: The musculoskeletal consequences and their etiology and pathogenesis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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