Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Schulz, AL; Albrecht, B; Arici, C; van der Burgt, I; Buske, A; Gillessen-Kaesbach, G; Heller, R; Horn, D; Hübner, CA; Korenke, GC; König, R; Kress, W; Krüger, G; Meinecke, P; Mücke, J; Plecko, B; Rossier, E; Schinzel, A; Schulze, A; Seemanova, E; Seidel, H; Spranger, S; Tuysuz, B; Uhrig, S; Wieczorek, D; Kutsche, K; Zenker, M.
Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.
Clin Genet. 2008; 73(1):62-70
Web of Science PubMed FullText FullText_MUG


Autor/innen der Med Uni Graz:
Plecko Barbara
Uhrig Sabine

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Plum Analytics:
Cardio-facio-cutaneous (CFC) and Costello syndrome (CS) are congenital disorders with a significant clinical overlap. The recent discovery of heterozygous mutations in genes encoding components of the RAS-RAF-MAPK pathway in both CFC and CS suggested a similar underlying pathogenesis of these two disorders. While CFC is heterogeneous with mutations in BRAF, MAP2K1, MAP2K2 and KRAS, HRAS alterations are almost exclusively associated with CS. We carried out a comprehensive mutation analysis in 51 CFC-affected patients and 31 individuals with CS. Twelve different BRAF alterations were found in twenty-four patients with CFC (47.0%), two MAP2K1 mutations in five (9.8%) and two MAP2K2 sequence variations in three CFC-affected individuals (5.9%), whereas three patients had a KRAS alteration (5.9%). We identified four different missense mutations of HRAS in twenty-eight cases with CS (90.3%), while KRAS mutations were detected in two infants with a phenotype meeting criteria for CS (6.5%). In 14 informative families, we traced the parental origin of HRAS alterations and demonstrated inheritance of the mutated allele exclusively from the father, further confirming a paternal bias in the parental origin of HRAS mutations in CS. Careful clinical evaluation of patients with BRAF and MAP2K1/2 alterations revealed the presence of slight phenotypic differences regarding craniofacial features in MAP2K1- and MAP2K2-mutation positive individuals, suggesting possible genotype-phenotype correlations.
Find related publications in this database (using NLM MeSH Indexing)
Abnormalities, Multiple - genetics
Adult -
Child -
DNA Mutational Analysis -
Developmental Disabilities -
Facies -
Heart Defects, Congenital - genetics
Humans -
Intellectual Disability -
MAP Kinase Kinase 1 - genetics
MAP Kinase Kinase 2 - genetics
Mutation -
Phenotype -
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins B-raf - genetics
Proto-Oncogene Proteins p21(ras) -
Skin Abnormalities - genetics
Syndrome -
ras Proteins - genetics

Find related publications in this database (Keywords)
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