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.

Matrix metalloproteinases (MMPs) are implicated in atherosclerotic plaque rupture and recondition. Specific tissue inhibitors (TIMPs) control MMP functions. Both MMPs and TIMPs are potential biomarkers of plaque instability. Elevated Apo‐CII and CIII and Apo‐E levels are recognized as cardiovascular disease risk factors. We aimed to establish the best blood biomarker panel to evaluate the coronary artery disease (CAD) severity. Plasma levels of MMP‐3 and MMP‐9, TIMP‐1 and TIMP‐2, Apo‐CII, Apo‐CIII and Apo‐E were measured in 472 patients with CAD evaluated by coronary angiography and electrocardiography, and in 285 healthy controls. MMP‐3 and MMP‐9 plasma levels in CAD patients were significantly increased ( P < 0.001) compared to controls (3.54‐ and 3.81‐fold, respectively). Furthermore, these increments are modulated by CAD severity as well as for Apo‐CII and Apo‐CIII levels ( P < 0.001). TIMPs levels were decreased in CAD versus controls ( P < 0.001) and in inverse correlation to MMPs. Standard ROC curve approach showed the importance of panels of biomarkers, including MMP‐3, MMP‐9, TIMP‐1, TIMP‐2, Apo‐CII and Apo‐CIII, for disease aggravation diagnosis. A high area under curve (AUC) value (0.995) was reached for the association of MMP‐9, TIMP‐2 and Apo‐CIII. The unbalance between MMPs and TIMPs in vascular wall and dyslipidaemia creates favourable conditions for plaque disruption. Our study suggests that the combination of MMP‐9, TIMP‐2 and Apo‐CIII values (‘CAD aggravation panel’) characterizes the severity of CAD, that is electrophysiological state, number of involved vessels, stent disposal and type of stent.

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