Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome

Pablo Rodriguez-Viciana, Osamu Tetsu, William E. Tidyman, Anne L. Estep, Brenda A. Conger, Molly Santa Cruz, Frank McCormick, Katherine A Rauen

Research output: Contribution to journalArticle

405 Citations (Scopus)

Abstract

Cardio-facio-cutaneous (CFC) syndrome is a sporadic developmental disorder involving characteristic craniofacial features, cardiac defects, ectodermal abnormalities, and developmental delay. We demonstrate that heterogeneous de novo missense mutations in three genes within the mitogen-activated protein kinase (MAPK) pathway cause CFC syndrome. The majority of cases (18 out of 23) are caused by mutations in BRAF, a gene frequently mutated in cancer. Of the 11 mutations identified, two result in amino acid substitutions that occur in tumors, but most are unique and suggest previously unknown mechanisms of B-Raf activation. Furthermore, three of five individuals without BRAF mutations had missense mutations in either MEK1 or MEK2, downstream effectors of B-Raf. Our findings highlight the involvement of the MAPK pathway in human development and will provide a molecular diagnosis of CFC syndrome.

Original languageEnglish (US)
Pages (from-to)1287-1290
Number of pages4
JournalScience
Volume311
Issue number5765
DOIs
StatePublished - Mar 3 2006
Externally publishedYes

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Germ-Line Mutation
Mitogen-Activated Protein Kinases
Missense Mutation
Mutation
Genes
Human Development
Amino Acid Substitution
Neoplasms
Cardiofaciocutaneous syndrome

ASJC Scopus subject areas

  • General

Cite this

Rodriguez-Viciana, P., Tetsu, O., Tidyman, W. E., Estep, A. L., Conger, B. A., Cruz, M. S., ... Rauen, K. A. (2006). Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science, 311(5765), 1287-1290. https://doi.org/10.1126/science.1124642

Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. / Rodriguez-Viciana, Pablo; Tetsu, Osamu; Tidyman, William E.; Estep, Anne L.; Conger, Brenda A.; Cruz, Molly Santa; McCormick, Frank; Rauen, Katherine A.

In: Science, Vol. 311, No. 5765, 03.03.2006, p. 1287-1290.

Research output: Contribution to journalArticle

Rodriguez-Viciana, P, Tetsu, O, Tidyman, WE, Estep, AL, Conger, BA, Cruz, MS, McCormick, F & Rauen, KA 2006, 'Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome', Science, vol. 311, no. 5765, pp. 1287-1290. https://doi.org/10.1126/science.1124642
Rodriguez-Viciana P, Tetsu O, Tidyman WE, Estep AL, Conger BA, Cruz MS et al. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science. 2006 Mar 3;311(5765):1287-1290. https://doi.org/10.1126/science.1124642
Rodriguez-Viciana, Pablo ; Tetsu, Osamu ; Tidyman, William E. ; Estep, Anne L. ; Conger, Brenda A. ; Cruz, Molly Santa ; McCormick, Frank ; Rauen, Katherine A. / Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. In: Science. 2006 ; Vol. 311, No. 5765. pp. 1287-1290.
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