A severe clinical phenotype of Noonan syndrome with neonatal hypertrophic cardiomyopathy in the second case worldwide with RAF1 S259Y neomutation
| Autor: | Sonia Blibech, Lilia Kraoua, Sonia Abdelhak, Laurent Argiro, R. M’rad, Heather C. Etchevers, Hager Jaouadi, Amel Ben Chehida, Nicolas Lévy, Rym Benkhalifa, Neji Tebib, Nadia Kasdallah, Valérie Delague, Stéphane Zaffran |
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| Přispěvatelé: | Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory (LR11IPT05), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Hôpital La Rabta [Tunis], Université de Tunis El Manar (UTM), Hôpital Charles Nicolle [Tunis], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital militaire de Tunis, Military Hospital of Tunis, Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Institut Pasteur de Tunis, The project leading to this publication has received funding from the Excellence Initiative of Aix-Marseille University – A*MIDEX, a French ‘Investissements d'Avenir’ programme (RARE-MED project)., The authors would like to thank the family for their collaboration. This work was supported by the Tunisian Ministry of Public Health, the Ministry of Higher Education and Scientific Research (LR16IPT05)., ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011) |
| Rok vydání: | 2019 |
| Předmět: |
Pathology
RAF1 mutation 030204 cardiovascular system & hematology medicine.disease_cause whole exome sequencing Exon 0302 clinical medicine [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] Noonan syndrome Exome sequencing 2. Zero hunger 0303 health sciences Mutation Hypertrophic cardiomyopathy General Medicine 3. Good health Phenotype Failure to thrive RAS/MAPK pathway Female medicine.symptom Research Paper medicine.medical_specialty Tunisia macromolecular substances Protein Serine-Threonine Kinases Polymorphism Single Nucleotide 03 medical and health sciences [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Pectus excavatum Proto-Oncogene Proteins Genetics medicine Humans cardiovascular diseases [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs 030304 developmental biology [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics Genetic heterogeneity business.industry Infant Cardiomyopathy Hypertrophic hypertrophic cardiomyopathy medicine.disease Proto-Oncogene Proteins c-raf [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics business [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology |
| Zdroj: | Genetics Research Genetics Research, Cambridge University Press (CUP), 2019, 101, pp.e6. ⟨10.1017/S0016672319000041⟩ |
| ISSN: | 1469-5073 0016-6723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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