Corpus callosum defect with dilated lateral ventricles and an occipital cyst in an Egyptian child with Diamond-Blackfan anemia

Diamond-Blackfan anemia (DBA), an inherited bone marrow failure syndrome characterized by anemia that usually presents before the first birthday or in early childhood, is associated with birth defects and an increased risk of cancer. Although anemia is the most prominent feature of DBA, the disease is also characterized by growth retardation and congenital malformations, in particular craniofacial, upper limb, heart, and urinary system defects that are present in approximately 30%-50% of patients. Herein, we present a patient with Diamond-Blackfan anemia associated craniofacial anomalies, pyramidal manifestations and corpus callosum defect and dilated lateral ventricles opening with each other and opening with a posterior occipital cyst, an association that to date has not been reported.Key Words: Diamond-Blackfan anemia, corpus callosum, dilated ventricles, occipital cyst

Case Report: Multiple pterygium syndrome with marked pterygia of the fingers and MRI changes in the spine

We report a two years old Egyptian girl, the first birth of consanguineous marriage with clinical findings consistent with the diagnosis of the autosomal recessive multiple pterygium syndrome (Escobar) (growth retardation, craniofacial dysmorphism, multiple pterygia, kyphoscoliosis, multiple joint contractures especially affecting the lower limbs). What characterizes out patient was the extensive pterygia of the fingers which kept them permanently flexed, while they were very mild in the neck, axillary folds and knee joints. Our patient suffered also from mental retardation although mentality is commonly reported to be normal in this syndrome. MRI of the spine revealed widened spinal canal and engorged intraspinal vessels, which were not reported before.Keywords: Multiple pterygium syndrome; Joint contractures; Kyphoscoliosis; Autosomal recessiv

Exploring The Effects Of Genetic Variation On Gene Regulation In Cancer In The Context Of 3D Genome Structure

Background Numerous genome-wide association studies (GWAS) conducted to date revealed genetic variants associated with various diseases, including breast and prostate cancers. Despite the availability of these large-scale data, relatively few variants have been functionally characterized, mainly because the majority of single-nucleotide polymorphisms (SNPs) map to the non-coding regions of the human genome. The functional characterization of these non-coding variants and the identification of their target genes remain challenging. Results In this communication, we explore the potential functional mechanisms of non-coding SNPs by integrating GWAS with the high-resolution chromosome conformation capture (Hi-C) data for breast and prostate cancers. We show that more genetic variants map to regulatory elements through the 3D genome structure than the 1D linear genome lacking physical chromatin interactions. Importantly, the association of enhancers, transcription factors, and their target genes with breast and prostate cancers tends to be higher when these regulatory elements are mapped to high-risk SNPs through spatial interactions compared to simply using a linear proximity. Finally, we demonstrate that topologically associating domains (TADs) carrying high-risk SNPs also contain gene regulatory elements whose association with cancer is generally higher than those belonging to control TADs containing no high-risk variants. Conclusions Our results suggest that many SNPs may contribute to the cancer development by affecting the expression of certain tumor-related genes through long-range chromatin interactions with gene regulatory elements. Integrating large-scale genetic datasets with the 3D genome structure offers an attractive and unique approach to systematically investigate the functional mechanisms of genetic variants in disease risk and progression

Case Report: Bilateral absence of fifth ray in feet, cleft palate, malformed ears, and corneal opacity in a patient with Miller syndrome

Background: Miller syndrome is one of the acrofacial dysostosis syndromes, which are characterized by malformations of the craniofacial region and limbs.Case report: A 26 month old male child, the product of healthy nonconsanguineous parents has many typical features of Miller syndrome. He has cleft lip and palate, malar hypoplasia, left crumpled cup shaped ear, and prominent nose together with the absence of the fifth ray in feet (postaxial) and fixation of interphalangeal joints of both thumbs (preaxial). However the limb affection is bilateral and symmetrical against what is usually reported (bilateral with more affection of one side) and the micrognathia is very mild. Our patient has also bilateral corneal opacities as well as underdeveloped external genitals.Conclusion: There is phenotypic variability in Miller syndrome, and our patient may represent a new distinct subgroup in postaxial acrofacial dysostosis.Keywords: Miller syndrome; Gene´e–Weidemann syndrome; Postaxial acrofacial dysostosis syndrome; Corneal opacit

Maternal risk factors in young Egyptian mothers of Down syndrome

Introduction: We investigated the possible maternal risk factors that mayincrease the incidence of Down syndrome (DS) in young Egyptian mothers(younger than 35 years) especially methylene tetrahydrofolate reductase(MTHFR) enzyme C677T polymorphism.Subjects and Methods: The study included 200 mothers of karyotypicallyascertained non-disjunction DS attending Genetics clinic, Children’s hospital, Ain Shams University (100 mothers were < 35 years and 100 mothers ≥ 35 years). 50 mothers of none-DS children served as a control group. For all cases, history was taken laying stress on: Parental ages at conception, maternal grandparent’s ages at conception of mother, DS birth order, history of oral contraceptive use 6 months before conception, genital infection, vitamin supplementation and smoking or exposure to irradiation.Results: MTHFR C677T mutational analysis was done to twenty DS motherswith ages ≤ 35 years revealed that 35% of young mothers had C677T mutation (10% had homozygous mutation and 25% had heterozygous mutation). MTHFR C677T polymorphism was found to be a possible maternal genetic risk factor for DS although statistically non-significant.Other maternal risk factors included the use of oral contraceptive pills (OCP) 6 months before pregnancy which was significantly higher only in DSmothers ≥ 35 years. on the other hand, parental consanguinity, maternal grandparents’ ages, the presence of genital infection and birth order did not show a significant difference between young and old mothers of DS.Conclusion: MTHFR C677T could not be considered as a maternal risk factor in young Egyptian mothers of DS. The risk effect may depend on gene-environment interaction between the genotype and dietary intake in particular folic acid consumption which should be further studied on a larger scale population including other MTHFR polymorphisms and environmental factors. Other risk factors may include the use of OCP in older mothers. Parents consanguinity, paternal age and maternal grandparents’ ages were not found to be risk factors in DS in this study.Keywords: Down syndrome, risk factors, mothers, MTHFR

Evaluation of serum kallistatin level as a predictor of esophageal varices in cirrhotic patients

Introduction: The Baveno VI consensus recommended the use of noninvasive predictors to identify patients at high risk of esophageal varices (EV) in whom endoscopic evaluation is most needed. Kallistatin is a protein molecule synthesized by the liver, and its level declines with the deterioration of liver functions. We aim to explore the role of kallistatin as a predictor of esophageal varices. Methods: This case–control study included 70 cirrhotic patients (35 patients with EV and 35 patients without EV). The laboratory investigations and upper GI endoscopy were performed, and the serum kallistatin level was measured in all patients. Results: The mean level of serum kallistatin was significantly lower in patients with varices (12.2 ± 5.6 vs 16.9 ± 4.8 μg/ml, p = 0.009). It also shows a significant decline in patients with large varices. Kallistatin can predict the presence of EV and large EV at cut off values of 15.8 and 8.9 μg/ml, respectively, with sensitivity and specificity of 71.4% and 54.3% for EV and 50% and 94.8% for large EV. Discussion: Kallistatin is a promising marker that can be used to predict the presence of esophageal varices especially when they are large and risky

Pregnancy Protects Hyperandrogenemic Female Rats from Postmenopausal Hypertension

Polycystic ovary syndrome, the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenemia, obesity, insulin resistance, and elevated blood pressure. However, few studies have focused on the consequences of pregnancy on postmenopausal cardiovascular disease and hypertension in polycystic ovary syndrome women. In hyperandrogenemic female (HAF) rats, the hypothesis was tested that previous pregnancy protects against age-related hypertension. Rats were implanted with dihydrotestosterone (7.5 mg/90 days, beginning at 4 weeks and continued throughout life) or placebo pellets (controls), became pregnant at 10 to 15 weeks, and pups were weaned at postnatal day 21. Dams and virgins were then aged to 10 months (still estrous cycling) or 16 months (postcycling). Although numbers of offspring per litter were similar for HAF and control dams, birth weights were lower in HAF offspring. At 10 months of age, there were no differences in blood pressure, proteinuria, nitrate/nitrite excretion, or body composition in previously pregnant HAF versus virgin HAF. However, by 16 months of age, despite no differences in dihydrotestosterone, fat mass/or lean mass/body weight, previously pregnant HAF had significantly lower blood pressure and proteinuria, higher nitrate/nitrite excretion, with increased intrarenal mRNA expression of endothelin B receptor and eNOS (endothelial nitric oxide synthase), and decreased ACE (angiotensin-converting enzyme), AT1aR (angiotensin 1a receptor), and endothelin A receptor than virgin HAF. Thus, pregnancy protects HAF rats against age-related hypertension, and the mechanism(s) may be due to differential regulation of the nitric oxide, endothelin, and renin-angiotensin systems. These data suggest that polycystic ovary syndrome women who have experienced uncomplicated pregnancy may be protected from postmenopausal hypertension.Fil: Shawky, Noha M.. University Of Mississippi Medical Center; Estados UnidosFil: Patil, Chetan N.. Medical College Of Wisconsin; Estados UnidosFil: Dalmasso, Carolina. University of Kentucky; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Instituto de Investigación Médica Mercedes y Martín Ferreyra. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa; ArgentinaFil: Marañón, Rodrigo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina; ArgentinaFil: Romero, Damián Gastón. University Of Mississippi Medical Center; Estados UnidosFil: Drummond, Heather. University Of Mississippi Medical Center; Estados UnidosFil: Reckelhoff, Jane F.. University Of Mississippi Medical Center; Estados Unido

Comparative analysis of the genes UL1 through UL7 of the duck enteritis virus and other herpesviruses of the subfamily Alphaherpesvirinae

The nucleotide sequences of eight open reading frames (ORFs) located at the 5' end of the unique long region of the duck enteritis virus (DEV) Clone-03 strain were determined. The genes identified were designated UL1, UL2, UL3, UL4, UL5, UL6 and UL7 homologues of the herpes simplex virus 1 (HSV-1). The DEV UL3.5 located between UL3 and UL4 had no homologue in the HSV-1. The arrangement and transcription orientation of the eight genes were collinear with their homologues in the HSV-1. Phylogenetic trees were constructed based on the alignments of the deduced amino acids of eight proteins with their homologues in 12 alpha-herpesviruses. In the UL1, UL3, UL3.5, UL5 and UL7 proteins trees, the branches were more closely related to the genus Mardivirus. However, the UL2, UL4, and UL6 proteins phylogenetic trees indicated a large distance from Mardivirus, indicating that the DEV evolved differently from other viruses in the subfamily Alphaherpesvirinae and formed a single branch within this subfamily