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A severe clinical phenotype of Noonan syndrome with neonatal hypertrophic cardiomyopathy in the second case worldwide with RAF1 S259Y neomutation
- Hager Jaouadi, Amel Ben Chehida, Lilia Kraoua, Heather C. Etchevers, Laurent Argiro, Nadia Kasdallah, Sonia Blibech, Valérie Delague, Nicolas Lévy, Néji Tebib, Ridha Mrad, Sonia Abdelhak, Rym Benkhalifa, Stéphane Zaffran
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- Journal:
- Genetics Research / Volume 101 / 2019
- Published online by Cambridge University Press:
- 29 April 2019, e6
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- Article
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Noonan syndrome and related disorders are a group of clinically and genetically heterogeneous conditions caused by mutations in genes of the RAS/MAPK pathway. Noonan syndrome causes multiple congenital anomalies, which are frequently accompanied by hypertrophic cardiomyopathy (HCM). We report here a Tunisian patient with a severe phenotype of Noonan syndrome including neonatal HCM, facial dysmorphism, severe failure to thrive, cutaneous abnormalities, pectus excavatum and severe stunted growth, who died in her eighth month of life. Using whole exome sequencing, we identified a de novo mutation in exon 7 of the RAF1 gene: c.776C > A (p.Ser259Tyr). This mutation affects a highly conserved serine residue, a main mediator of Raf-1 inhibition via phosphorylation. To our knowledge the c.776C > A mutation has been previously reported in only one case with prenatally diagnosed Noonan syndrome. Our study further supports the striking correlation of RAF1 mutations with HCM and highlights the clinical severity of Noonan syndrome associated with a RAF1 p.Ser259Tyr mutation.
12 - Genetics of human susceptibility to infection and hepatic disease caused by schistosomes
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- By Alain J. Dessein, Immunologie et Génétique des Maladies Parasitaires, Institut National de la Santé et de la Recherche Médicale, Laboratoire de Parasitologie-Mycologie, Faculté de Médecine, Marseille, France, Sandrine Marquet, Immunologie et Génétique des Maladies Parasitaires, Institut National de la Santé et de la Recherche Médicale, Laboratoire de Parasitologie-Mycologie, Faculté de Médecine, Marseille, France, Carole Eboumbou Moukoko, Immunologie et Génétique des Maladies Parasitaires, Institut National de la Santé et de la Recherche Médicale, Laboratoire de Parasitologie-Mycologie, Faculté de Médecine, Marseille, France, Hèlia Dessein, Immunologie et Génétique des Maladies Parasitaires, Institut National de la Santé et de la Recherche Médicale, Laboratoire de Parasitologie-Mycologie, Faculté de Médecine, Marseille, France, Laurent Argiro, Immunologie et Génétique des Maladies Parasitaires, Institut National de la Santé et de la Recherche Médicale, Laboratoire de Parasitologie-Mycologie, Faculté de Médecine, Marseille, France, Sandrine Henri, Immunologie et Génétique des Maladies Parasitaires, Institut National de la Santé et de la Recherche Médicale, Laboratoire de Parasitologie-Mycologie, Faculté de Médecine, Marseille, France, Dominique Hillaire, Immunologie et Génétique des Maladies Parasitaires, Institut National de la Santé et de la Recherche Médicale, Laboratoire de Parasitologie-Mycologie, Faculté de Médecine, Marseille, France, Christophe Chevillard, Immunologie et Génétique des Maladies Parasitaires, Institut National de la Santé et de la Recherche Médicale, Laboratoire de Parasitologie-Mycologie, Faculté de Médecine, Marseille, France, Nasureldin El Wali, Institute of Nuclear Medicine and Molecular Biology, University of Gezira, Wad Medani, Sudan, Mubarak Magzoub, Institute of Nuclear Medicine and Molecular Biology, University of Gezira, Wad Medani, Sudan, Laurent Abel, Génétique Humaine des Maladies Infectieuses, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Necker, Paris, Virmondes Rodrigues, Jr, Faculty of Medicine do Triangulo Mineiro, Ubéraba, Brazil, Aluizio Prata, Faculty of Medicine do Triangulo Mineiro, Ubéraba, Brazil, Gachuhi Kimani, Kenya Medical Research Institute, Biomedical Sciences Research Centre, Nairobi, Kenya
- Edited by Richard Bellamy, Kintampo Health Research Centre, Ghana
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- Book:
- Susceptibility to Infectious Diseases
- Published online:
- 14 August 2009
- Print publication:
- 22 December 2003, pp 337-360
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Summary
Schistosome infections cause much suffering in millions of people living in tropical regions of Africa, Asia, and South America (Prata, 1987; Chitsulo et al., 2000). The most severe clinical symptoms affect the kidneys and urinary tract. However, schistosomes also cause various other disorders such as heart failure and neurological diseases. Three species of schistosome are responsible for most human infections (Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium). These species are found in different geographical locations, have different vectors, and cause different symptoms. Schistosomes are multicellular parasites that are disseminated as free swimming larvae (cercariae) in ponds, lakes, and rivers by snails. Humans become infected when they stay in contaminated water for a few minutes. The cercariae penetrate the human skin and develop into male or female adult schistosomes within 5 or 6 weeks. These small worms (Fig. 12.1A) can live in the vascular system of their vertebrate host for 2 to 5 years. Schistosomes do not multiply within their vertebrate host. The female worms, however, lay hundreds of eggs per day in the mesenteric or vesical veins of their host. Most of the symptoms associated with these infections are caused by the inflammation that is induced by the immunogenic and toxic substances produced by the eggs. The chronic cellular reaction that develops around the eggs is organised in a granuloma (Von Lichtenberg, 1962; Warren et al., 1967).