Prenatal diagnosis of dent disease type I with a nonsense pathogenic variant in CLCN5: a case study.

INTRODUCTION: Dent disease type I is a rare X-linked recessive renal tubular disease resulting from pathogenic variants in the CLCN5 gene. Due to the rarity of Dent disease type I and the diversity of its phenotypes, its clinical diagnosis is complex and poses a challenge to clinicians. METHODS: A foetus and a child from a 36-year-old pregnant woman with a birth history of abnormal children were enrolled in this study. Pregnant women undergo amniocentesis for prenatal diagnosis at the gestational age of 12+ 3 weeks. Chromosomal microarray (CMA) analysis and whole-exome sequencing (WES) were employed to investigate the chromosomal copy number and single gene variants. Literature retrieval and data analysis were performed for genotype and phenotype collection analysis. RESULTS: No chromosomal abnormalities or CNVs were detected in the entire family through karyotype and familial CMA analyses. WES identified a nonsense pathogenic variant in CLCN5 of the X chromosome, c.1942 C > T (exon 11, NM_000084), which was inherited from his mother, who exhibited regular clinical features. CONCLUSION: This study suggests that children with low-molecular-weight proteinuria and hypercalciuria should undergo prompt genetic testing to exclude Dent disease.

Eugenol-Mediated Inhibition of Biofilm Formed by S. aureus: a Potent Organism for Pediatric Digestive System Diseases.

Ocimum tenuiflorum (KT) is a common ethnobotanical plant of Southeast Asia. The ethnic communities of these regions use the various parts of the plants, especially the leaves, for the treatment of various ailments like cold and flu, chronic infections, and surface ailments. The leaves of these plants are consumed to act as immune boosters in the body. With this ethnical background, we performed the antimicrobial and antibiofilm potential of the methanolic extract of Ocimum tenuiflorum against biofilm formed by S. aureus biofilm. The biofilm formed by S. aureus is a potent cause for the development of gastrointestinal (GI)-associated chronic infection. The extract from the KT leaf was analyzed using UV spectroscopy and HPLC to confirm the presence of the active ingredients present within the extract. The HPLC and GC-MS studies revealed the presence of eugenol and linalool in a greater proportion having the maximum drug-like properties. It was observed that KT showed maximum inhibition of biofilms, proteins, and carbohydrates being present with the extracellular polymeric substance (EPS). Interestingly, the maximum inhibition to the quorum sensing (QS) and the genomic DNA, RNA content was reduced by eugenol and linalool in comparison to the plant extract. The studies were supported by in silico interaction between eugenol and linalool with the QS proteins of S. aureus. The studies were further confirmed with microscopic studies SEM and FCM. The IR studies also confirmed much reduction in biofilm when treated with eugenol, linalool, and KT with respect to the untreated sample.

Renal Tissue Damage Induced by Acute Kidney Injury in Sepsis Rat Model Is Inhibited by Cynaropicrin via IL-1ß and TNF-α Down-Regulation.

Acute kidney injury (AKI), one of the frequently diagnosed and serious sepsis induced complication has high morbidity and mortality. The present study investigated the effect of cynaropicrin on AKI induced pathological damage in rat model in vivo. Treatment with cynaropicrin suppressed AKI induced urea nitrogen and creatinine in the rat serum in dose-dependent manner. Development of sepsis mediated renal injury in rats was also effectively prevented on treatment with cynaropicrin. Secretion of AKI-induced IL-1ß and TNF-α in renal tissues was alleviated significantly in rats by cynaropicrin treatment. Additionally, in cynaropicrin-treated rats renal tissues AKI induced Bax expression was alleviated while as Bcl-2 was promoted compared to AKI rats. Cynaropicrin treatment improved the survival rate of the rats with AKI. Cynaropicrin inhibits renal tissue damage and increase survival rate in AKI rat model. The mechanism involves alleviation of inflammatory cytokine secretion and promotion of Bcl­2 expression. Thus, cynaropicrin may be used as therapeutic agent for treatment of AKI.

Discordance of cardiovascular abnormalities in a monozygotic twin pair carrying a class II 1q21.1 microdeletion.

OBJECTIVE: We present the prenatal diagnosis of a class II 1q21.1 microdeletion in monozygotic (MZ) twins with discordant phenotypes. CASE REPORT: A monochorionic diamniotic twin pair presented with discordant ultrasound anomalies; twin A had cardiovascular abnormalities, while twin B did not. No specific complications were noted in the twins during pregnancy. A single nucleotide polymorphism array revealed an identical class II 1q21.1 microdeletion inherited from a phenotypically normal mother and identified the twins as MZ. The deleted region encompassed both the proximal 1q21.1 thrombocytopenia absent radius syndrome region and the distal 1q21.1 recurrent microdeletion region. No other rare copy number variants (CNVs) were identified, and concordance was observed in the CNVs between the twins. CONCLUSION: Discordant cardiovascular abnormalities may occur in MZ twins carrying the same class II 1q21.1 microdeletion. Further studies involving discordant MZ twins are needed to determine the modifying factors of the phenotypic heterogeneity of the microdeletion.

Is an analysis of copy number variants necessary for various types of kidney ultrasound anomalies in fetuses?

BACKGROUND: This study aimed to estimate the associations of copy number variants (CNVs) with fetal kidney ultrasound anomalies. A total of 331 fetuses with kidney ultrasound anomalies who underwent prenatal chromosomal microarray analyses were enrolled. The fetuses were classified into groups with isolated and nonisolated anomalies or according to the types of kidney anomalies. RESULTS: Clinically significant CNVs were identified in 3.4% or 7.3% of fetuses with isolated or nonisolated kidney anomalies, respectively. CNVs were more frequently identified in fetuses with abnormal embryonic migration of the kidneys (6.6%) than in fetuses with malformations of the renal parenchyma (4.7%) or anomalies of the urinary collecting system (3.4%). In particular, CNVs were most frequently detected in fetuses with ectopic kidneys (9.5%) but not in fetuses with horseshoe kidneys or isolated duplex kidneys. Among these CNVs, the most common were del(17)(q12q12) (1.2%) and del(22)(q11q11) (0.6%). The dup(17)(p12p12) and del(15)(q11.2q11.2) CNVs were identified in this study but not in previous studies. The del(X)(p11.4p11.4) and del(16)(p13.3p13.3) CNVs were further implicated as associated with kidney anomalies. CONCLUSIONS: Fetuses with abnormal embryonic migration of the kidneys (particularly ectopic kidneys) showed a higher frequency of clinically significant CNVs, whereas fetuses with horseshoe kidneys or duplex kidneys were less frequently associated with these CNVs.

Clinical and molecular cytogenetic studies of an unrecognised 22q11.2 deletion in three families.

The phenotypic variability associated with 22q11.2 deletion syndrome (22q11.2DS) is well known. In the present study, the cases of three unrelated adult patients with chromosome 22q11.2DS and nearly normal features are described, along with their reproductive histories. Chromosomal analysis with fluorescent in situ hybridisation and genomic DNA analysis by microarrays were performed, as well as a clinical examination. The three patients were found to possess an identical breakpoint deletion at 22q11.2 by high-density whole-genome single nucleotide polymorphism microarray analysis. The patients had histories of two foetuses/infants with congenital heart defects. The underlying aetiology for the discordance in the phenotype in these patients is discussed. These observations provide additional data useful for patient counselling and guidelines for 22q11.2 clinical screening.

[Quantitative analysis of cerebellar vermis in fetuses with Dandy-Walker syndrome with three-dimensional ultrasonography].

OBJECTIVE: To evaluate the third plane image of the three-dimensional sonography (3D US) for the quantitative analysis of the cerebellar vermis in normal and Dandy-Walker syndrome (DWS) fetuses. METHODS: The cerebellar vermis was scanned with trans-abdominal 3D US in the second and third trimesters in 571 normal fetuses and 39 fetuses with Dandy-Walker syndrome. The surface area of the vermis in the mid-sagittal view was measured and calculated. The correlation between the vermian area and the pregnant week was analyzed. The data of vermian area between normal and DWS fetuses was compared. RESULTS: The vermian area was measured in 529 normal fetuses in the third plane of 3D US. The vermis grew in a linear fashion throughout pregnancy and the growth pattern positively correlated with the gestational age (r2 = 0. 854, P < 0.05). In 39 fetuses with DWS, including 14 with Dandy-Walker malformation (DWM) and 25 with Dandy-Walker variant (DWV), no vermian structure was showed in the mid-sagittal plane in 12 fetuses with DWM and 2 fetuses with DWV, whereas a small vermis appeared in other DWSs. CONCLUSIONS: The third plane image obtained by 3D US is valuable in studying the fetal cerebellar vermis during the middle and late pregnancy. Knowledge of normal and abnormal vermian appearance may help identify developmental anomalies. Measurement of vermian area in the third plane with 3D US provide a quantitative indicator for prenatal diagnosis of DWS.