Determination of Carrier Frequency of Actionable Pathogenic Variants in Autosomal Recessive Genetic Diseases in the Turkish Cypriot Population.

Whole-exome DNA sequencing is a rich source of clinically useful information for specialists, patients, and their families, as well as elucidating the genetic basis of monogenic and complex diseases in clinical diagnosis. However, interpreting and reporting variants encompassing exome and genome sequence analysis outcome data are one of the greatest challenges of the genomic era. In this study, we aimed to investigate the frequency and allele frequency spectrum of single nucleotide variants accepted as recessive disease carrier status in Turkish Cypriot exomes. The same sequencing platform and data processing line were used for the analysis of data from 100 Turkish Cypriot whole-exome sequence analysis. Identified variants were classified according to ACMG guidelines, and pathogenic variants were confirmed in other databases such as ClinVar, HGMD, Varsome, etc. Pathogenic variants were detected in 68 genes out of 100 whole-exome sequence data. The carriage rate was the highest in the CYP21A2 gene, causing 21-hydroxylase deficiency (14.70%), 11.76% in the HBB gene causing ß-thalassemia, 10.29% in the BTD gene causing biotinidase deficiency, 8.82% in the CFTR gene causing cystic fibrosis, 8.82% in the RBM8A gene causing thrombocytopenia-absent radius syndrome, which is an ultra-rare disease, and 5.88% in the GAA gene causing glycogen storage disease II. The carriage of pathogenic variants in other genes causing the disease (GJB2, PAH, GALC, CYP11B2, COL4A3, HBA1, etc.) was determined as less than 5.00%. Also, the identified variations in the mentioned gene within the examined population were reported. The most prevalent mutation in North Cyprus was a missense variant (c.1360 C>T, p.Pro454Ser) detected in the CYP21A2 gene (rs6445), and the most frequently seen variant in the HBB gene was c.93-21G>A (rs35004220). We investigated reported pathogenic variants by estimating the lower and upper limits of carrier and population frequencies for autosomal recessive diseases, for which exome sequencing may reveal additional medically relevant information. Determining the lower and upper limits of these frequencies will shed light on preventive medicine practices and governmental actions.

Is there any link between vitamin D deficiency and vasovagal syncope?

BACKGROUND: This study aimed to investigate serum 25[OH]D levels between patients with vasovagal syncope (VVS) diagnosed with head-up tilt table test (HUTT) and age-matched healthy people. METHODS: The study included 75 consecutive patients (32.3 ± 10.7 years), who presented with syncope and underwent HUTT and 52 healthy controls (32.9 ± 14.1 years). HUTT patients were divided into two groups according to whether there was syncope response to the test. Patients underwent cardiac, psychiatric, and neurological investigation. Serum 25[OH]D levels were measured by chemiluminescent microparticle immunoassay method. RESULTS: There was no difference between the two groups in terms of age, gender, body mass index (BMI), echocardiographic findings (P > .05). Mean serum 25[OH]D (24.5 ± 6.3 vs 20.1 ± 8.8 ng/mL, P = .003) and vitamin B12 levels (436.4 ± 199.2 vs 363.1 ± 107.6 pg/mL, P = .009) was lower in syncope patients when compared to the control group. In correlation analyses, syncope was shown as correlated with the vitamin D (r = -264, P = .003) and vitamin B12 levels (r = -233, P = .009). But, multivariate regression analyses showed that only vitamin D increased risk of syncope [OR: 0.946, 95% CI (0.901-0.994)]. There was no difference in terms of age, gender, BMI, echocardiographic findings between the in HUTT positive (n = 45) and negative groups (n = 29). Only vitamin D level was significantly lower in HUTT positive group (17.5 ± 7.7 vs 24.4 ± 9.1 ng/mL, P = .002). There was no difference among in the vasovagal subgroups in terms of vitamin D level and other features. CONCLUSION: Vitamin D and B12 levels were reasonably low in syncope patients, but especially low Vitamin D levels were associated with VVS diagnosed in HUTT.

Improvement of abnormal systolic motion of the interventricular septum with cardiac resynchronization therapy.

BACKGROUND: There is no consensus in the literature regarding what is the responsible mechanism of left ventricular dyssynchrony; septal dyskinesia or late movement of left ventricle (LV) lateral wall. We aim to evaluate the abnormal systolic motion in each myocardial segment and the improvement of LV systolic function with pulsed tissue Doppler imaging (TDI) in patients undergoing cardiac resynchronization therapy (CRT) with left bundle branch block (LBBB). METHODS: A total of 26 patients undergoing CRT implantation with LBBB, wide QRS duration (≥120 ms), and low ejection fraction (EF) (<35%) were included. Pulsed TDI was taken from apical 4-chamber view and parasternal short axis view (PSAX). All echocardiographic parameters were measured when CRT is on and off. RESULTS: Systolic ejection time (ET) of anteroseptal and posterolateral wall of LV in PSAX was statistically significantly longer in CRT on group (321.6 ± 62.7 vs 237.5 ± 59.3 ms, P < .001; 323.9 ± 58.0 vs 289.4 ± 43.7 ms, P = .015, respectively). In apical 4-chamber view, septal annulus systolic ET is significantly longer in CRT on group than CRT off group (315.8 ± 57.2 vs 287.3 ± 42.2, P = .014). Also, there was a strong correlation between systolic ET of the septum in PSAX with aortic velocity time integral (VTI), QRS duration and EF (r = .587, P = .002; r = .479, P = .013; r = .440, P = .025; respectively). CONCLUSION: Circumferential contraction of septal myocardial fibers is improved with CRT and it is strongly correlated with increase of aortic VTI and shortening of QRS duration. These findings predict the deterioration of septal contraction as the main mechanism in patients with LBBB pattern and, CRT may improves myocardial contraction by correcting septal systolic motion.

Isolated Persistent Left Superior Vena Cava, Sick Sinus Syndrome, and Challenging Pacemaker Implantation.

Persistent left superior vena cava with absent right superior vena cava is a very rare venous anomaly and is known as isolated PLSVC. It is usually an asymptomatic anomaly and is mostly detected during difficult central venous access or pacemaker implantation, though it could also be associated with an increased incidence of congenital heart disease, arrhythmias, and conduction disturbances. Herein, we describe a dual-chamber pacemaker implantation in a patient with isolated PLSVC and sick sinus syndrome.

The relation between vitamin B12 and SYNTAX score.

BACKGROUND: Vitamin B12 is required in the metabolism of homocysteine. Vitamin B12 deficiency has been implicated in endothelial dysfunction and cardiovascular disease via hyperhomocysteinaemia. However, the association of vitamin B12 and the severity of coronary artery disease has not been studied to date. AIM: This study was conducted with the aim of evaluating the relationship between vitamin B12 and SYNTAX score. METHODS: Medical records of consecutive patients who underwent coronary artery bypass grafting surgery were retrospectively reviewed. The study group consisted of 127 patients. Vitamin B12, other biochemical parameters, clinical and echocardiographic parameters, and SYNTAX score were evaluated for all patients. RESULTS: Patients with vitamin B12 deficiency had a higher prevalence of cardiovascular risk factors such as diabetes mellitus, and history of transient ischaemic attack/stroke and heart failure. The SYNTAX score was significantly higher in patients with vitamin B12 deficiency (29.2 ± 4.9 vs. 22.5 ± 4.5, p < 0.05). CONCLUSIONS: In our study, we found a significant relationship between vitamin B12 deficiency and SYNTAX score, demon-strating the severity and complexity of coronary artery disease.

Is SYNTAX Score Predictive of Atrial Fibrillation after On-Pump Coronary Artery Bypass Graft Surgery?

BACKGROUND AND OBJECTIVES: The relationship of synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score and development of atrial fibrillation (AF) after coronary artery bypass surgery (CABG) has not been studied. Therefore, we assessed the relationship between the SYNTAX score and development of AF after CABG (POAF). SUBJECTS AND METHODS: The medical records of consecutive patients, who underwent CABG surgery from January 2013 to September 2015, were retrospectively reviewed for the development of AF in the postoperative period. SYNTAX score, clinical and echocardiographic parameters were evaluated. The independent variables for the development of POAF were defined and their predictive values were measured. RESULTS: The study group consisted of 106 patients, of which 36 (34%) developed POAF. Age, hypertension, stroke, chronic obstructive pulmonary disease (COPD), heart failure (HF), diabetes mellitus (DM), left atrial diameter, neutrophil/lymphocyte ratio, platelet large cell ratio, creatinine, blood urea nitrogen and SYNTAX score were identified as important variables for the development of POAF. However, in logistic regression analysis COPD (OR=19.313, 95% CI=2.416-154.407, p=0.005), HF (OR=28.362, 95% CI=2.034-395.515, p=0.013), SYNTAX score (OR=0.863, 95% CI=0.757-0.983, p=0.026), and DM (OR=20.770, 95% CI=3.791-113.799, p<0.001) appeared as independent variables predicting the development of POAF. In receiver operation characteristic analysis, SYNTAX score (≥22.25) (AUC=0.777, 95% CI=0.676-0.877, p<0.001) was one of the strongest predictors for the development of POAF. CONCLUSION: The SYNTAX score level was independently associated with the development of AF after CABG.

Kink of Subclavian Artery Mimicking Stenosis.

The treatment for subclavian artery stenosis includes the more common endovascular therapy rather than surgical intervention in symptomatic patients. We present a case of a 79-year-old man with coronary artery bypass graft where subclavian artery stenosis was found incidentally. In this asymptomatic case, we have merged clinical and multiple imaging modalities to secure the diagnosis and treatment plan.