Publication Date:
2006-01-28
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rodriguez-Viciana, Pablo -- Tetsu, Osamu -- Tidyman, William E -- Estep, Anne L -- Conger, Brenda A -- Cruz, Molly Santa -- McCormick, Frank -- Rauen, Katherine A -- HD048502/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2006 Mar 3;311(5765):1287-90. Epub 2006 Jan 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Comprehensive Cancer Center and Cancer Research Institute, University of California, San Francisco, CA 94115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16439621" target="_blank"〉PubMed〈/a〉
Keywords:
Abnormalities, Multiple/*genetics
;
Adolescent
;
Adult
;
Amino Acid Substitution
;
Child
;
Child, Preschool
;
Craniofacial Abnormalities/genetics
;
Extracellular Signal-Regulated MAP Kinases/metabolism
;
Female
;
*Germ-Line Mutation
;
Growth Disorders/genetics
;
Heart Defects, Congenital/genetics
;
Humans
;
Infant
;
MAP Kinase Kinase 1/genetics
;
MAP Kinase Kinase 2/genetics
;
MAP Kinase Kinase Kinases/metabolism
;
MAP Kinase Signaling System
;
Male
;
Mitogen-Activated Protein Kinases/genetics/*metabolism
;
Mutation, Missense
;
Phosphorylation
;
Proto-Oncogene Proteins B-raf/genetics
;
Skin Abnormalities/genetics
;
Syndrome
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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