👤 Semra Gürsoy

Dyggve-Melchior-Clausen (DMC) syndrome is a rare autosomal recessive skeletal dysplasia caused by mutations in the We reported three siblings with DMC syndrome. Two 4-year-old monozygotic male twins, born to consanguineous parents, presented with growth retardation and developmental delay. Radiographs showed generalized platyspondyly, rhizomelic shortening and metaphyseal dysplasia, while biochemical tests excluded MPS IV. Molecular tests revealed a homozygous deletion in exon 16 of the The clinical and radiological features of our patients were consistent with DMC syndrome, with partial overlap with MPS IV. This case series represents the first reported coexistence of DMC and Down syndrome. In addition, we identified a novel homozygous deletion in exon 16 of the Show less

Advanced age is a well-recognized risk factor for atherosclerotic cardiovascular disease (ASCVD). Given the ongoing debate regarding the initiation of statin therapy in elderly individuals, identifying those with underlying coronary artery disease (CAD) who may benefit from lipid-lowering treatment is essential. This study aimed to identify predictors of CAD in statin-naïve adults aged ≥ 70 years with elevated low-density lipoprotein cholesterol (LDL-C), with particular emphasis on risk assessment, cumulative LDL-C burden, and lipoprotein(a) [Lp(a)] levels. The analysis included consecutive patients aged ≥ 70 years with LDL-C ≥ 160 mg/dL, available Lp(a) measurements, no prior history of ASCVD or diabetes, who underwent evaluation for CAD by coronary imaging or functional stress testing. Global ASCVD risk was estimated using the Systematic Coronary Risk Estimation 2-Older Persons (SCORE2-OP) and the Spanish Familial Hypercholesterolemia Cohort Study (SAFEHEART) risk scores. A total of 202 patients were included (mean age 76 years; 68.3% female). CAD was diagnosed in 30.7% of participants. In multivariable analysis, male sex (odds ratio [OR]: 2.109), Lp(a) level (OR: 1.012 per mg/dL), and cumulative LDL-C (OR: 1.155 per g/dL) were independently associated with CAD. The highest CAD prevalence was observed among individuals with cumulative LDL-C ≥ 14 g/dL and Lp(a) ≥ 50 mg/dL. While the SCORE2-OP algorithm failed to predict CAD, the SAFEHEART risk score was significantly associated with CAD. In statin-naïve elderly individuals with elevated LDL-C levels, male sex, cumulative LDL-C exposure, and high Lp(a) levels were independently associated with CAD. These findings underscore the potential utility of incorporating cumulative LDL-C and Lp(a) into risk stratification for older adults. Show less

Prosthetic valve thrombosis (PVT) is a critical and life-threatening condition driven by multifactorial etiologies, including genetic predispositions. The study was designed as a single-center retrospective manner. Echocardiographic features and genetic test including factor II/prothrombin (G20210A), factor V Leiden (G1691A), factor V R2 (A4070G), apolipoprotein (Apo) B-100 (G10708A), ApoE (C112R), ApoE (R158C), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, factor XIII G103T (V34L), β-fibrinogen (455G>A), PAI-1 4G/5G, and HPA-1 GPIIIa (T196C) genotyping variations were assessed. We performed genetic tests on 175 patients with PVT (biologically women [n = 124, 70.9%], with a mean age of 49.8 ± 13.1 years) and 101 patients (biologically women [n = 57, 56.4%], with a mean age of 54.7 ± 13.6 years) without thrombus formation. The thrombosis group was significantly younger compared with controls (p = 0.004). The percentage of patients with mechanical aortic valves was significantly lower in the thrombosis group compared with controls (22.3% vs 34.7%, p = 0.025). A significant difference was observed between the thrombosis and control groups regarding the genotype ratios of factor II/prothrombin (G20210A) (heterozygous, 6.8% vs 1%, p = 0.043) and HPA-1 GPIIIa (T196C) (homozygous mutant, 7.8% vs 0%, p = 0.034). In addition, there was a significant association of heterozygous MTHFR (A1298C) variation with obstructive thrombosis compared with nonobstructive thrombosis (46.9% vs 29.2%, p = 0.046). In conclusion, this is the first study to report a potential association between genetic variants, including HPA-1 GPIIIa (T196C), factor II/prothrombin (G20210A), MTHFR (A1298C), and PVT, necessitating extensive further research and additional clinical consideration. Show less

Genetic and numerous epidemiologic studies have identified lipoprotein (a) [Lp(a)] as a risk factor for atherothrombotic diseases. The structure of Lp(a) is similar to plasminogen and tissue plasminogen activator and it competes with plasminogen for its binding site, leading to reduced fibrinolysis. Furthermore, since Lp(a) stimulates the secretion of plasminogen activator inhibitor-1, it may lead to thrombogenesis. In this cross-sectional study, we aimed to investigate Lp(a) levels in patients with mechanical prosthetic valve thrombosis (MPVT). Blood samples for Lp(a) determination were obtained from 80 MPVT patients (median age: 48.5 (39-59.75) years; 47 male) and 75 age and sex matched controls (median age: 52 (39-63) years; 44 male) with normally functioning mechanical prosthetic valves. The Lp(a) levels in the PVT group were significantly higher than in the controls [22(16.2-39.4) vs. 6.9(2.9-24.6) mg/dL, p < 0.001]. Elevated Lp(a) levels, recent history of subtherapeutic anticoagulation, history of cerebrovascular accidents (CVA) and a low value of international normalized ratio on admission were found to be the independent predictors of PVT. Lp(a) levels above 19.6 mg/dL predicted PVT with a sensitivity of 65% and a specificity of 71% (AUC:0.767; 95%CI: 0.687 to 0.847; p < 0.001). Lp(a) levels were significantly higher in PVT patients with a history of CVA [42.0 (23.6-53.6) vs. 21.1 (16.1- 36.2) mg/dL, p = 0.012]. Elevated Lp(a) levels may be associated with MPVT. The assessment of plasma Lp(a) levels in patients with prosthetic heart valves may provide additive information regarding the risk of PVT and CVA. Show less

Non-syndromic monogenic obesity is a rare cause of early-onset severe obesity in the childhood period. The aim of this study was to screen four obesity related genes ( Next-generation sequencing of all exons in Fifteen different variants in nineteen patients were identified with a variant detection rate of 12.3%. While six different heterozygous variants were observed in In conclusion, MC4R variants are the most common genetic cause of monogenic early-onset obesity, consistent with the literature. The c.496G>A variant in Show less