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In the era of the diseasomes and interactome networks, linking genetics with phenotypic traits in Turner syndrome should be studied thoroughly. As a part of this stratagem, mosaicism of both X and Y chromosome which is a common finding in TS and an evaluation of congenital heart diseases in the different situations of mosaic TS types, can be helpful in the identification of disturbed sex chromosomes, genes and signaling pathway actors. Here we report the case of a mosaic TS associated to four left-sided CHD, including BAV, COA, aortic aneurysms and dissections at an early age. The mosaicism included two cell lines, well-defined at the cytogenetic and molecular levels: a cell line which is monosomic for Xp and Xq genes (45,X) and another which is trisomic for pseudoautosomal genes that are present on the X and Y chromosomes and escape X inactivation: 45,X[8]/46,X,idic(Y)(pter→q11.2::q11.2→pter)[42]. This case generates two hypotheses about the contribution of genes linked to the sex chromosomes and the signaling pathways involving these genes, in left-sided heart diseases. The first hypothesis suggests the interaction between X chromosome and autosomal genes or loci of aortic development, possibly dose-dependent, and which could be in the framework of TGF-β-SMAD signaling pathways. The second implies that left-sided congenital heart lesions involve sex chromosomes loci. The reduced dosage of X chromosome gene(s), escaping X inactivation during development, contributes to this type of CHD. Regarding our case, these X chromosome genes may have homologues at the Y chromosome, but the process of inactivation of the centromeres of the isodicentric Y spreads to the concerned Y chromosome genes. Therefore, this case emerges as an invitation to consider the mosaics of Turner syndrome and to study their phenotypes in correlation with their genotypes to discover the underlying developmental and genetic mechanisms, especially the ones related to sex chromosomes.

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.

The effects of subchronic exposure to tetradifon on biochemical related kidney toxicological parameters [creatinine (CRT), urea, and uric acid (UA)] were examined. Oxidative stress in kidney tissue was also assessed by measuring vitamin C (VitC) content and antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)]. Tetradifon was administered orally to 12 rats at a cumulative dose of 24.3 mg/kg for 12 weeks. Twelve additional rats, no treated, have served as control. Control and treated animals were sacrificed after 6 or 12 weeks. For each group, kidneys were examined for morphometric changes. Results showed that tetradifon induced significant increases in CRT and urea, and decrease in UA. Morphometrically, while mean glomerular volume decreased percentage of sclerosed glomeruli increased in treated rats. Index of interstitial fibrosis was significantly higher. Moreover, renal antioxidant enzyme (SOD and GPx) activities and VitC content decreased. We concluded that tetradifon possessed nephrotoxic by promoting kidney morphometric and functional damage and depleting renal antioxidant defense system in rats., (Copyright © 2010 Elsevier GmbH. All rights reserved.)