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Shereen Abdelghaffar,1 Hassan Shora,2 Sahar Abdelatty,3 Fatma Elmougy,3 Reham El Sayed,3 Heba Abdelrahman,3 Hend Soliman,1 HebatAllah Algebaly,1 Sakinatalfouad Ahmed,1 Peter Alfy,1 Yasmine Elshiwy3 1Department of Pediatrics, Cairo University, Cairo, Egypt; 2Department of Molecular Biology/Biochemistry, Port Said University, Port Said, Egypt; 3Department of Clinical and Chemical Pathology, Cairo University, Cairo, EgyptCorrespondence: Shereen AbdelghaffarDepartment of Pediatrics, Faculty of Medicine, Cairo University, Cairo, EgyptTel +201005859252Fax +201272202209Email kshereen@kasralainy.edu.egPurpose: Currently available markers for early detection of diabetic nephropathy (DN), the leading cause of end stage renal disease, have some limitations. There is insufficient evidence from previous studies about the role of several circulating microRNAs (miRNAs) in the early development of DN. This study aimed to describe the expression of miRNA-377, miRNA-93, miRNA-25, miRNA-216a, and miRNA-21 in a sample of type 1 diabetic children and adolescents to explore their association with DN and some indices of kidney injury.Patients and Methods: Seventy type 1 diabetic patients, with 5 years’ duration of diabetes or more, were recruited from Children’s Hospital, Faculty of Medicine, Cairo University. Quantitative real-time reverse-transcription PCR (qRT-PCR) was used to measure the expression of the above mentioned miRNAs in serum and to assess its association with DN, and the studied risk factors.Results: There was a significantly higher percentage of up-regulation of miRNA-377 and miRNA-93 (P=0.03, 0.02, respectively) in addition to significant down-regulation of miRNA-25 (P=0.01) in patients with DN than in patients without DN. In patients with DN, expression of miR-216a was significantly negatively correlated with creatinine (r=− 0.4, P=0.04) and positively correlated with eGFR using creatinine (r=0.5, P=0.03). In the same group, expression of miR-21 was positively correlated with urinary cystatin C (r=0.6, P=0.01) and was negatively correlated with e-GFR using cystatin c (r=− 0.6, P=0.01). miRNA-93 was associated with increased risk (odds ratio=15, 95% CI=12.03– 24.63, P=0.01), while miRNA-25 was associated with decreased risk for albuminuria (odds ratio=0.15, 95% CI=0.08– 0.55, P=0.03).Conclusion: miRNA-377, miRNA-93, miRNA-216a, and miRNA-21 may be implicated in the pathogenesis of DN, while miRNA-25 may have a reno-protective role. More studies are needed to document the value of these miRNAs as diagnostic biomarkers as well as therapeutic targets in DN.Keywords: microRNAs, type 1 diabetes, diabetic nephropathy, albuminuria, children

Background: Congenital adrenal hyperplasia (CAH) is a monogenic disorder caused by genetic diversity in the CYP21A2 gene, with 21-hydroxylase deficiency (21-OHD) as the most common type. Early sex assignment and early diagnosis of different genetic variations with a proper technique are important to reduce mortality and morbidity. Proper early sex identification reduces emotional, social, and psychological stress. Aim: Detection of a spectrum of aberrations in the CYP21A2 gene, including copy number variations, gene conversion, chimeric genes, and point variations. Methods: The CYP21A2 gene was screened using MLPA assay in 112 unrelated Egyptian children with 21-OHD CAH (33 males and 79 females). Results: In the studied group, 79.5% were diagnosed within the first month of life. 46.8% of the genetic females were misdiagnosed as males. Among the copy number variation results, large deletions in 15.4% and three types of chimeric genes in 9% (CH-1, CH-7, and CAH-X CH-1) were detected. Regarding gene dosage, one copy of CYP21A2 was found in 5 cases (4.5%), three copies were detected in 7 cases (6.3%), and one case (0.9%) showed four copies. Eight common genetic variants were identified, I2G, large deletions, large gene conversion (LGC), I172N, F306 + T, -113 SNP, 8bp Del, and exon 6 cluster (V237E and M239K) with an allelic frequency of 32.62%, 15.45%, 7.30%, 3.00%, 2.58%, 2.15%, 0.86%, and 0.86%, respectively. Conclusion: High prevalence of copy number variations highlights the added value of using MLPA in routine laboratory diagnosis of CAH patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tolba, Mandour, Musa, Elmougy, Hafez, Abdelatty, Ibrahim, Soliman, Labib, Elshiwy, Ramzy and Elsharkawy.)

Background and Study Aims: Pruritus is an annoying symptom with an unclear pathogenesis accompanied by chronic cholestasis. This cross-sectional study was conducted to define the relationship between serum levels of presumed pruritogens (bile acids (BAs) and serotonin) and severity of pruritus in pediatric patients with chronic cholestatic liver disease., Patients and Methods: A total of 28 children suffering from pruritus due to chronic cholestatic liver disease and 29 age- and sex-matched healthy control subjects were examined. Scores obtained used the 5-D itch scale were evaluated among patients. Serum levels of BAs and serotonin were determined using enzymatic assays and high-performance liquid chromatography, respectively., Results: Patients had higher serum BA levels and lower serotonin levels than control subjects. Serum BA levels were significantly elevated in 61% of patients. The 5-D itch scale scores were significantly higher in cholestatic individuals with normal γ-glutamyl transpeptidase levels. Neither BA nor serotonin levels correlated with the severity of the 5-Ditch scale score., Conclusion: Neither BA nor serotonin levels correlated with the severity of pruritus, indicating that they may not be good laboratory markers for the intensity of itch in children with cholestasis. Our findings suggest that it is necessary to identify another potential pruritogenic mediator, most probably of a biliary origin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

CYP21A2 genotyping remains an important element in the diagnosis and management of congenital adrenal hyperplasia, and establishing accurate genotype-phenotype correlations has facillitated adequate genetic counseling and prenatal management for at-risk families. Despite extensive efforts to establish a clear genotype-phenotype correlation, some discordance remains. Establishing a diagnosis of congenital adrenal hyperplasia on the basis of biochemical and clinical data is occasionally challenging, and the identification of CYP21A2 mutations may help confirm the diagnosis. We review the diagnostic challenges despite an extensive genetic evaluation for 14 patients with a suspected clinical and biochemical diagnosis of congenital adrenal hyperplasia. Other diagnostic entities should be considered in the absence of convincing genetic data., (© 2017 New York Academy of Sciences.)

We investigated the association of the Osteopontin (OPN) (rs9138 and rs1126616) polymorphisms with colorectal cancer (CRC). One hundred CRC patients and 112 healthy individuals were subjected to OPN (rs9138 and rs1126616) genotyping and measurement of OPN protein plasma level. The C allele of OPN rs1126616 and the CC haplotype were significantly higher in CRC patient (p = 0.036, 0.003, respectively). In females, the C allele of OPN rs9318 (A/C) polymorphism was significantly associated with increased CRC risk (p = 0.036). The plasma OPN level >104.35 ng/mL was significantly associated with CRC. Our findings suggest a significant role played by OPN (rs9138 and rs1126616) in colorectal carcinogenesis.