Evaluation of coronary artery abnormalities in Williams syndrome patients using myocardial perfusion scintigraphy and CT angiography

Background: Sudden death risk in Williams syndrome (WS) patients has been shown to be 25–100 times higher than in the general population. This study aims to detect coronary artery anomalies and myocardial perfusion defects in WS patients using noninvasive diagnostic methods. Methods: This study features 38 patients diagnosed with WS. In addition to physical examination, electrocardiography, and echocardiography, computed tomography (CT) angiography and rest/dipyridamole stress technetium-99m sestamibi (99mTc-sestamibi) single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy (MPS) were performed. Results: Twenty-one (55%) patients were male; 17 (45%) were female. The average patient age was 12 ± 5 years (2.5–26 years); the average follow-up period was 7.2 ± 4.2 years (6 months–18 years). Cardiovascular abnormalities were found in 89% of patients, the most common one being supravalvar aortic stenosis (SVAS). CT angiography revealed coronary anomalies in 10 (26%) patients, the most common ones being ectasia of the left main coronary artery and proximal right coronary artery as well as myocardial bridging. SVAS was present in 80% of patients with coronary artery anomalies. 99mTc-sestamibi SPECT MPS revealed findings possibly consistent with myocardial ischemia in 29% of patients, and ischemia in 7 out of 10 patients (70%) with coronary anomalies shown on CT angiography (p = 0.03). Conclusions: Coronary artery abnormalities are relatively common in WS patients and are often accompanied by SVAS. CT angiography and dipyridamole 99mTc-sestamibi SPECT MPS seem to be less invasive methods of detecting coronary artery anomalies and myocardial perfusion defects in WS patients

Trichothiodystrophy-associated MPLKIP maintains DBR1 levels for proper lariat debranching and ectodermal differentiation

The brittle hair syndrome Trichothiodystrophy (TTD) is characterized by variable clinical features, including photosensitivity, ichthyosis, growth retardation, microcephaly, intellectual disability, hypogonadism, and anaemia. TTD-associated mutations typically cause unstable mutant proteins involved in various steps of gene expression, severely reducing steady-state mutant protein levels. However, to date, no such link to instability of gene-expression factors for TTD-associated mutations in MPLKIP/TTDN1 has been established. Here, we present seven additional TTD individuals with MPLKIP mutations from five consanguineous families, with a newly identified MPLKIP variant in one family. By mass spectrometry-based interaction proteomics, we demonstrate that MPLKIP interacts with core splicing factors and the lariat debranching protein DBR1. MPLKIP-deficient primary fibroblasts have reduced steady-state DBR1 protein levels. Using Human Skin Equivalents (HSEs), we observed impaired keratinocyte differentiation associated with compromised splicing and eventually, an imbalanced proteome affecting skin development and, interestingly, also the immune system. Our data show that MPLKIP, through its DBR1 stabilizing role, is implicated in mRNA splicing, which is of particular importance in highly differentiated tissue.</p

Transcri̇pti̇on of Umdetu'l - Hakayık volume I

1838 yılında İstanbul'da doğan Süleyman Hüsnü Paşa, Harbiye Mektebi'nden mezun olmasının ardından Karadağ Harekâtına katılmıştır. İlk görevi bu askeri harekât olan Süleyman Hüsnü Paşa, burada Derviş Mehmet Paşa kuvvetlerine katılmıştır. İskorbüt ve bağırsak hastalıkları ile uğraşan, morali bozuk ve sürekli şikâyet eden askerlerden oluşan taburlarla karşılaşan Süleyman Hüsnü Paşa, kendini iki görev mükellef görür. Bunlaradan birincisi, askerin sıhhat ve afiyetine çalışmak; İkincisi ise askerin ahlak yapısı ve moralini düzeltmekti. Umdetü'l-Hakayık adlı eserinde Karadağ harekâtının askeri cephesini zafer ve çekişmeleri ile birinci elden kaynak olarak karşımıza çıkarmaktadır.Süleyman Hüsnü Pasha, born in 1838 in İstanbul, participated to the Karadağ (Montenegro) Campaign following his graduation from Harbiye Mektebi (School of Warfare). In his first mission, Süleyman Hüsnü Pasha joined here to the forces of Derviş Mehmet Pasha. Encountering with soldiers who were suffering from scurvy and indestinal diseases, demoralized and in a constant state of complaint, Süleyman Hüsnü Pasha considered himself charged with two missions. First, try to improve health and mood of soldiers; and second, restore their manner and moral. In his work, Umdetu'l-Hakayık, he presented the military aspect of Karadağ Campaign with its victories and struggles as a primary source

Örnek olgularla array uygulamalarında karşılaşılan sorunlar ve çözüm önerileri

Cytogenetics, molecular cytogenetics and a-CGH / microarray techniques are complementary tools, operated within the sophisticated combination of equations in connection to clinical indications, time-frames, availability of resources, experienced specialist, and the accessibility ofthe family members if required to be included in the investigation for meaningful results; should not be considered within the irrational hopes. In the last 40 years, the diagnostic sensitivity of chromosomal anomalies has increased from megabases (Mb) to kilobases (kb), with the use of new techniques applied in parallel to novel technological developments. In particular, the development and clinical application of a-CGH in recent years has revolutionized the diagnostic management of patients and greatly facilitated the identification of the molecular basis of many genetic diseases. Due to these developments, molecular karyotyping began to replace the classical cytogenetic techniques in patients with mental retardation and / or congenital anomalies and in prenatal cases with abnormal ultrasound findings.Besides all these diagnostic advantages, there are some disadvantages such as erroneous or incidental probe hybridization or unexplored results of detections. In this context, it is necessary to develop appropriate algorithms for our country and to know the limitations of the technique thoroughly. In this presentation, discussion environment will be conceived and experiences will be shared along with the case illustrations