Molecular genetic diagnostics in syndromes associated with the RAS/MAPK signalling pathway

Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række
Anders MolvenTrine E Prescott

Abstract

Mutations in genes of the mitogen-activated protein kinase (MAPK) cascade have recently been shown to cause several syndromes characterized by dysmorphic facial features, growth retardation, cognitive impairment, heart disease and cutaneous abnormalities. This signalling pathway involves RAS and RAF proteins, and is central in the regulation of normal growth and the development of cancer. We have studied 23 Norwegian patients for whom there was a clinical suspicion of Costello, Noonan or cardio-facio-cutaneous syndrome. Patients suspected of having Noonan syndrome had previously tested negative for mutations in the tyrosine phosphatase gene PTPN11. The material was examined for mutations in the HRAS, KRAS, RAF1 and BRAF genes. Two patients are described to illustrate diagnostic challenges and the usefulness of genetic testing. Ten of 23 patients (43 %) had mutations affecting the RAS/MAPK signalling pathway. Mutations in HRAS were most common (five cases), while three patients had mutations in KRAS and two in RAF1. Spontaneous mutations were demonstrated in eight cases. Our data indicate an annual incidence of 1-2 new cases of congenital RAS/RAF mutations in Norway. Upon clinical suspicion of syndromes of the RAS/MAPK signallin...Continue Reading

References

Jun 1, 1977·Australian Paediatric Journal·J M Costello
Oct 1, 1968·American Journal of Diseases of Children·J A Noonan
Feb 1, 2003·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Raoul C M Hennekam
Jul 13, 2005·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Karen W Gripp
Sep 20, 2005·Nature Genetics·Yoko AokiYoichi Matsubara
Jul 11, 2006·Journal of Medical Genetics·A RobertsG Neri
Sep 23, 2006·Archives of Disease in Childhood·A C ShawM A Patton
Feb 28, 2007·European Journal of Medical Genetics·Karen Helene ØrstavikTrine E Prescott
May 15, 2007·Oncogene·A S DhillonW Kolch
Jul 3, 2007·Nature Genetics·M Abdur RazzaqueRumiko Matsuoka
Aug 31, 2007·Nature Genetics·Andrew O M Wilkie
May 13, 2008·Human Mutation·Yoko AokiYoichi Matsubara
Dec 10, 2008·Expert Reviews in Molecular Medicine·William E Tidyman, Katherine A Rauen

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Citations

Jun 28, 2016·Clinical Linguistics & Phonetics·Magnhild Selås, Wenche Andersen Helland

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