Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome

Niihori, Tetsuya; Aoki, Yoko; Narumi, Yoko; Neri, Giovanni; Cavé, Hélène; Verloes, Alain; Okamoto, Nobuhiko; Hennekam, Raoul C. M.; Gillessen‐Kaesbach, Gabriele; Wieczorek, Dagmar; Kavamura, Maria Inês; Kurosawa, Kenji; Ohashi, Hirofumi; Wilson, Louise C.; Héron, Delphine; Bonneau, Dominique; Corona, Giuseppina; Kaname, Tadashi; Naritomi, Kenji; Baumann, Clarisse; Matsumoto, Naomichi; Kato, Kumi; Kure, Shigeo; Matsubara, Yoichi

doi:10.1038/ng1749

Cited by 543 publications

(527 citation statements)

References 14 publications

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“…CFC syndrome has been reported with supraventricular tachycardia [Rodriguez-Viciana et al, 2006], unspecified arrhythmia, or atrial tachycardia [Niihori et al, 2006;Narumi et al, 2007]. Because of the similarities, we hypothesize that the non-reentrant tachycardias will be identified in the other RASopathies.…”

Section: Comparison To Other Rasopathiesmentioning

confidence: 88%

Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: A Ras/MAPK pathway syndrome

Lin

Alexander

Colan

et al. 2011

American J of Med Genetics Pt A

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Cardiovascular abnormalities are important features of Costello syndrome and other Ras/MAPK pathway syndromes (“RASopathies”). We conducted clinical, pathological and molecular analyses of 146 patients with an HRAS mutation including 61 enrolled in an ongoing longitudinal study and 85 from the literature. In our study, the most common (84%) HRAS mutation was p.G12S. A congenital heart defect (CHD) was present in 27 of 61 patients (44%), usually non‐progressive valvar pulmonary stenosis. Hypertrophic cardiomyopathy (HCM), typically subaortic septal hypertrophy, was noted in 37 (61%), and 5 also had a CHD (14% of those with HCM). HCM was chronic or progressive in 14 (37%), stabilized in 10 (27%), and resolved in 5 (15%) patients with HCM; follow‐up data was not available in 8 (22%). Atrial tachycardia occurred in 29 (48%). Valvar pulmonary stenosis rarely progressed and atrial septal defect was uncommon. Among those with HCM, the likelihood of progressing or remaining stable was similar (37%, 41% respectively). The observation of myocardial fiber disarray in 7 of 10 (70%) genotyped specimens with Costello syndrome is consistent with sarcomeric dysfunction. Multifocal atrial tachycardia may be distinctive for Costello syndrome. Potentially serious atrial tachycardia may present in the fetus, and may continue or worsen in about one‐fourth of those with arrhythmia, but is generally self‐limited in the remaining three‐fourths of patients. Physicians should be aware of the potential for rapid development of severe HCM in infants with Costello syndrome, and the need for cardiovascular surveillance into adulthood as the natural history continues to be delineated. © 2011 Wiley‐Liss, Inc.

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Section: Comparison To Other Rasopathiesmentioning

confidence: 88%

Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: A Ras/MAPK pathway syndrome

Lin

Alexander

Colan

et al. 2011

American J of Med Genetics Pt A

Self Cite

117

106

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“…Recently, mutations in genes linked to MKK signaling have been associated with a group of human syndromes that includes cardiofacio-cutaneous (CFC) syndrome (mutations in KRas, MEK1, MEK2 and BRAF) (Niihori et al, 2006;Rodriguez-Viciana et al, 2006), Noonan syndrome (NS) and LEOPARD syndrome (LS), which are caused by gain-of-function mutations and inactivating mutations in the protein tyrosine phosphatase PTP11 (SHP2), leading to constitutive (Araki et al, 2004;Fragale et al, 2004) or impaired MAPK activation (Kontaridis et al, 2005), respectively, as well as Costello syndrome (CS), an autosomal dominant disease that has been linked to activating mutations in HRAS (Aoki et al, 2005;Estep et al, 2006). Each causes a similar array of phenotypic consequences including facial dysmorphia, abnormal growth and, notably in this context, cardiovascular defects.…”

Section: Mkk Signaling In Developmental Syndromesmentioning

confidence: 99%

MKK signaling and vascularization

et al. 2007

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In 1998, George Vande Woude's lab discovered that anthrax lethal factor (LF), the principal virulence component of anthrax toxin, was a zinc-metalloprotease that cleaved and inactivated mitogen-activated protein kinase kinases (MKK). It was perhaps not surprising, given the known roles of MKK1 and 2 in cell proliferation, that LF was subsequently found to dramatically inhibit tumor growth in vivo. What was not anticipated, however, was that the tumors treated with LF would have a substantially reduced vascular content. This intriguing result was one of the first indications that MKK signaling plays an important role in promoting tumor vascularization in vivo. In the following short review, we will compare in vitro and in vivo evidence that supports the hypothesis that MKK signaling pathways are essential for vascularization.

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“…PTPN11 mutations are also observed in about 90% of cases of a Noonan-like syndrome called LEOPARD syndrome (Digilio et al, 2002). Phenotypically overlapping Costelo syndrome and cardio-facio-cutaneous syndrome are caused by gain-of-function HRAS mutation and KRAS/BRAF/MEK1/MEK2 mutation, respectively (Aoki et al, 2005;Niihori et al, 2006;RodriguezViciana et al, 2006). Some Noonan syndrome cases are also attributed to gain-of-function mutations in SOS1 that encodes the RAS guanine nucleotide exchange factor or KRAS (Schubbert et al, 2006;Roberts et al, 2007;Tartaglia et al, 2007).…”

Section: Introductionmentioning

confidence: 99%