Rauen KA.. Distinguishing Costello versus cardio-facio-cutaneous syndrome: BRAF mutations in patients with a Costello phenotype. Am J Med Genet A 140: 1681-1683

Department of Pediatrics, Division of Medical Genetics, University of California, San Francisco, California, USA.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 08/2006; 140(15):1681-3. DOI: 10.1002/ajmg.a.31315
Source: PubMed
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    • "However, the association of CFC syndrome with cancer is rare (van Den Berg and Hennekam, 1999; Niihori et al., 2006; Rodriguez- Viciana et al., 2006). Two BRAF mutations have also been identified in individuals with Costello syndrome (CS), a syndrome similar to the CFC (Rauen, 2006). No BRAF E600 mutations have been identified in either CFC syndrome or CS patients so far. "
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    ABSTRACT: Of the RAF family of protein kinases, BRAF is the only member to be frequently activated by mutation in cancer. A single amino acid substitution (V600E) accounts for the vast majority and results in constitutive activation of BRAF kinase function. Its expression is required to maintain the proliferative and oncogenic characteristics of BRAF(E600)-expressing human tumour cells. Although BRAF(E600) acts as an oncogene in the context of additional genetic lesions, in primary cells it appears to be associated rather with transient stimulation of proliferation. Eventually, BRAF(E600) signalling triggers cell cycle arrest with the hallmarks of cellular senescence, as is illustrated by several recent studies in cultured cells, animal models and benign human lesions. In this review, we will discuss recent advances in our understanding of the role of BRAF(E600) in benign and malignant human tumours and the implications for therapeutic intervention.
    Preview · Article · Mar 2008 · Oncogene
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    • "The mutations were, however, located in different exons from the ones found previously in CFC syndrome patients. As in the case reported by Rauen (2006), the mutation in KRAS gene found in our patient is novel, not described previously in individuals with either NS or CFC syndrome. Therefore, the involvement of BRAF or, in our case, the KRAS gene in patients with CS suggests that these genes could also be responsible for a Costello phenotype, possibly with clinical findings less typical of CS, or, as in our case, with additional findings seen in NS. "
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    ABSTRACT: Costello syndrome is an autosomal dominant disorder comprising growth deficiency, mental retardation, curly hair, coarse facial features, nasal papillomata, low-set ears with large lobes, cardiac anomalies, redundant skin in palms and soles with prominent creases, dark skin, and propensity to certain solid tumors. HRAS mutations have been implicated in approximately 85% of the affected cases. The clinical overlap among Costello, Noonan, and cardiofaciocutaneous syndromes is now better understood given their common molecular background, such that all these syndromes constitute a class of disorders caused by deregulated RAS-MAPK signaling. We report on a novel KRAS gene mutation in a patient presenting the clinical features typical of Costello syndrome and the additional findings seen in Noonan syndrome. This description emphasizes that a subset of patients with Costello syndrome could harbor mutations in other genes involved in the RAS-MAPK signaling.
    Preview · Article · Feb 2007 · Journal of Human Genetics
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    ABSTRACT: Research based on Landsat image interpretation, GIS-topographic mapping,historical records, and ground truthing indicates that the evolution of the muddy coast and the expansion of the Pearl River delta have been strongly affected by human activities in historical times. In recent decades the region has experienced severe man-induced siltation coupled with rapid but premature reclamation of muddy tidal flats in the wake of economic development and population expansion.At present, there is practically no natural coastal landscape left, the shoreline beingcharacterized by man-made dikes throughout. In addition, most of the delta plain is poorly protected, being situated below local high-tide and storm-surge levels. The delta region is thus exposed to natural disasters such as typhoon-driven storm surges and ground subsidence caused by local sediment compaction and regional tectonics. These effects are compounded by the threat of accelerated relative sea-level rise which has been estimated to reach 0.5 m within the next 50 years. Without massive protection works this would lead to the inundation of 96.5% of the delta region, and would include the destruction of even entire cities such as Guangzhou.We contend that the effects of human interventions in the Pearl River delta region have reached the same significance as those associated with geological processes. This important aspect has to be taken into account when studying the recent evolution of the delta, especially when seeking sustainable solutions for the economic development of the region.
    No preview · Article · Dec 2000
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