Multiplex ligation-dependent probe amplification versus fluorescent in situ hybridization for screening RB1 copy number variations in Egyptian patients with retinoblastoma.

BACKGROUND: Retinoblastoma (RB) is the most common primary intraocular malignant tumor in children. RB is mostly caused by biallelic mutations in RB1 and occurs in hereditary and non-hereditary forms according to the "two-hit" theory. RB1 mutations comprise point mutations, indels, large deletions, and duplications. Genetic testing is essential for the comprehensive treatment and management of patients with RB. AIM: The aim was to evaluate RB1 copy number variations (CNVs) using MLPA versus FISH assays in group of Egyptian patients with RB. RESULTS: 16.67% showed an RB1 deletion, abnormal methylation status, or both. CONCLUSION: Our results suggested MLPA is a fast, reliable, and powerful method and should be used as a first-line screening tool for detecting RB1 CNVs in patients with RB. Moreover, MLPA is advantageous as it evaluates the methylation status/inactivation of RB1, not possible by FISH.

Interstitial Deletion of 2q22.2q22.3 Involving the Entire ZEB2 Gene in a Case of Mowat-Wilson Syndrome.

Mowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by dysmorphic features, mental retardation, and congenital heart disease (CHD). MWS results from microdeletions of chromosome 2q23 or de novo SNVs involving the ZEB2 gene. Here, we report on an Egyptian MWS patient diagnosed by chromosomal microarray (CMA). A 1-year-old male child was referred to the CHD clinic, National Research Centre, presenting with dysmorphic features and CHD. The patient was referred to the human cytogenetics department for cytogenetic analysis and for screening of subtelomere rearrangements and microdeletion loci, using MLPA, and all revealed normal results. CMA revealed an interstitial 2.27-Mb microdeletion in chromosome 2q, involving the entire ZEB2 gene and other genes. This study emphasizes the significance of CMA in the detection of microdeletions/microduplications and as a screening tool in cases presenting with CHD and extracardiac manifestations. MWS should be suspected in patients presenting with the characteristic facial dysmorphism, developmental delay, seizures, Hirschsprung disease, and congenital heart anomalies, especially those involving the pulmonary arteries or pulmonary valves. It is recommended to include the ZEB2 locus in the MLPA microdeletions probes.

Idiopathic Bradycardia in Unicuspid Unicommissural Aortic Valve Complicated with Infective Endocarditis and Aortic Root Abscess: A Case Report.

Unicuspid aortic valves are among the rarest congenital malformations. They are classified as either acommissural or unicommissural, with the unicommissural being presented in early adulthood. Unicuspid valves share many similarities with bicuspid valves, namely increased rates of valve degeneration and calcification, making them prone to secondary aortic stenosis, regurgitation, or both. Among other similarities are the increased risk of aortic root dilatation, dissection, and left ventricular dilatation. We report our case of a 23-year-old male with unicuspid unicommissural aortic valve with aortic root and left ventricular dilatation. He successfully underwent Wheat procedure.

Clinical and genetic characterization of ten Egyptian patients with Wolf-Hirschhorn syndrome and review of literature.

BACKGROUND: Wolf-Hirschhorn syndrome (WHS) (OMIM 194190) is a multiple congenital anomalies/intellectual disability syndrome. It is caused by partial loss of genetic material from the distal portion of the short arm of chromosome. METHODS: We studied the phenotype-genotype correlation. RESULTS: We present the clinical manifestations and cytogenetic results of 10 unrelated Egyptian patients with 4p deletions. Karyotyping, FISH and MLPA was performed for screening for microdeletion syndromes. Array CGH was done for two patients. All patients exhibited the cardinal clinical manifestation of WHS. FISH proved deletion of the specific WHS locus in all patients. MLPA detected microdeletion of the specific locus in two patients with normal karyotypes, while array CGH, performed for two patients, has delineated the extent of the deleted segments and the involved genes. LETM1, the main candidate gene for the seizure phenotype, was found deleted in the two patients tested by array CGH; nevertheless, one of them did not manifest seizures. The study emphasized the previous. CONCLUSION: WHS is a contiguous gene syndrome resulting from hemizygosity of the terminal 2 Mb of 4p16.3 region. The Branchial fistula, detected in one of our patients is a new finding that, to our knowledge, was not reported.

Evaluation of myocardial function in neonatal sepsis using tissue Doppler imaging.

Background: Neonatal sepsis is an important cause of neonatal morbidity and mortality especially in developing countries. Cardiac dysfunction is a major complication of severe sepsis and occurs as a part of multiple organ failure.Objective: To asses right and left ventricular functions in neonates with sepsis using tissue Doppler imaging (TDI).Methods: A total of 50 neonates fulfilling the diagnostic criteria for sepsis and 25 healthy neonates were enrolled in our study. Myocardial function and pulmonary systolic pressure were assessed using conventional echocardiography and tissue Doppler imaging techniques.Results: Septic neonates had a lower E/A ratio of the mitral valve when compared to healthy neonates (p = .048), indicating left ventricular diastolic dysfunction. Pulmonary systolic pressure was significantly higher in septic neonates compared to control group (p < .001). Left ventricular systolic function (left ventricular fractional shortening and S wave mitral annulus) was not significantly different between septic and healthy neonates. Left ventricular fractional shortening (LVFS) was found to be significantly higher in the survived than the nonsurvived septic neonates (p = .0387).Conclusions: Neonates with sepsis have evidence of left ventricular diastolic dysfunction and elevated pulmonary systolic pressure. Reduced left ventricular fractional shortening is associated with poor prognosis.

A Rare Case of Multiorgan Calciphylaxis in a Patient with Stage 5 Chronic Kidney Disease.

Calciphylaxis or calcific uremic arteriolopathy (CUA) is a potentially life-threatening vasculopathy involving the skin and subcutaneous tissues. It is usually associated with chronic kidney disease (CKD) and rarely with acute renal failure or predialysis patients. The clinical diagnosis of calcific uremic arteriolopathy relies on high index of suspicion. CUA is commonly associated with secondary hyperparathyroidism and high serum calcium and phosphate products. Moreover, using biopsy as a diagnostic tool is controversial, due to the high risk of poor wound healing and sepsis. Radiological studies usually reveal extensive calcification of branching vessels such as penile arteries, eventually leading to gangrene formation in extremities and penis. Histopathological analysis confirms the diagnosis of calcific uremic arteriolopathy and rules out the presence of malignancy. CUA is a systematic disease that involves multiple organs, and to the best of our knowledge this is the first reported case involving the penis, bladder, and eyes.