title: Clinical and Molecular Findings of Tunisian Patients with RASopathies.
abstract: Noonan syndrome (NS) and related disorders, which are now summarized under the term RASopathies, are caused by germline mutations in genes encoding protein components of the Ras/mitogen-activated protein kinase pathway. In this study, we evaluated the clinical and molecular spectrum of 21 Tunisian patients, recruited by a cardiology unit, for whom RASopathy diagnosis was suspected by clinical geneticists. Overall, 19 patients had a clinical diagnosis of NS and 2 were classified as having Cardiofaciocutaneous (CFC) syndrome. In 52% (n = 11) of patients, a RASopathy has been molecularly confirmed. Mutations in PTPN11 and SOS1 genes were found in patients with diagnosis of NS and BRAF gene mutations in patients with CFC syndrome. As reported from other cohorts, mutations in exons 3 and 8 of the PTPN11 gene predominated in Tunisian NS patients. A very uncommon PTPN11 mutation c.5C>T (p.T2I), the functional consequences of which have so far remained unclear, was identified in one patient. As biased by the mode of recruitment, all patients included in this study had a congenital heart defect, with pulmonary valve stenosis being the most frequent one. Short stature and developmental abnormalities were present in mutation-positive cases. This is the first molecular study in patients from southern Tunisia with RASopathy diagnosis.
authors.affiliation: Department of Histology, Medical University of Sfax, Center of Biotechnology of Sfax, Sfax, Tunisia.
authors.forename: Rim
authors.initials: R
authors.lastname: Louati
authors.affiliation: Department of Histology, Medical University of Sfax, Center of Biotechnology of Sfax, Sfax, Tunisia.
authors.forename: N Bouayed
authors.initials: NB
authors.lastname: Abdelmoula
authors.affiliation: Cardiology Service, Hedi Chaker Hospital, Center of Biotechnology of Sfax, Sfax, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Trabelsi
authors.affiliation: Cardiology Service, Hedi Chaker Hospital, Center of Biotechnology of Sfax, Sfax, Tunisia.
authors.forename: Dorra
authors.initials: D
authors.lastname: Abid
authors.affiliation: Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Lissewski
authors.affiliation: Laboratory of Microorganisms and Biomolecules, Center of Biotechnology of Sfax, Sfax, Tunisia.
authors.forename: Najla
authors.initials: N
authors.lastname: Kharrat
authors.affiliation: Cardiology Service, Hedi Chaker Hospital, Center of Biotechnology of Sfax, Sfax, Tunisia.
authors.forename: Samir
authors.initials: S
authors.lastname: Kamoun
authors.affiliation: Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenker
authors.affiliation: Department of Histology, Medical University of Sfax, Center of Biotechnology of Sfax, Sfax, Tunisia.
authors.forename: Tarek
authors.initials: T
authors.lastname: Rebai
keywords: BRAF; Cardiofaciocutaneous syndrome; Noonan syndrome; PTPN11; RASopathy; RIT1; SOS1