A severe clinical phenotype of Noonan syndrome with neonatal hypertrophic cardiomyopathy in the second case worldwide with RAF1 S259Y neomutation - Aix-Marseille Université Accéder directement au contenu
Article Dans Une Revue Genetics Research Année : 2019

A severe clinical phenotype of Noonan syndrome with neonatal hypertrophic cardiomyopathy in the second case worldwide with RAF1 S259Y neomutation

Résumé

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.
Fichier principal
Vignette du fichier
severe_clinical_phenotype_of_noonan_syndrome_with_neonatal_hypertrophic_cardiomyopathy_in_the_second_case_worldwide_with_raf1_s259y_neomutation.pdf (351.34 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-02461305 , version 1 (30-01-2020)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Hager Jaouadi, Amel Ben Chehida, Lilia Kraoua, Heather Etchevers, Laurent Argiro, et al.. A severe clinical phenotype of Noonan syndrome with neonatal hypertrophic cardiomyopathy in the second case worldwide with RAF1 S259Y neomutation. Genetics Research, 2019, 101, pp.e6. ⟨10.1017/S0016672319000041⟩. ⟨hal-02461305⟩
72 Consultations
129 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More