Copy Number Variation Analysis Facilitates Identification of Genetic Causation in Patients with Congenital Anomalies of the Kidney and Urinary Tract.

Background: Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of chronic kidney disease among children and adults younger than 30 yr. In our previous study, whole-exome sequencing (WES) identified a known monogenic cause of isolated or syndromic CAKUT in 13% of families with CAKUT. However, WES has limitations and detection of copy number variations (CNV) is technically challenging, and CNVs causative of CAKUT have previously been detected in up to 16% of cases.

Mutations of the Transcriptional Corepressor ZMYM2 Cause Syndromic Urinary Tract Malformations.

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute one of the most frequent birth defects and represent the most common cause of chronic kidney disease in the first three decades of life. Despite the discovery of dozens of monogenic causes of CAKUT, most pathogenic pathways remain elusive. We performed whole-exome sequencing (WES) in 551 individuals with CAKUT and identified a heterozygous de novo stop-gain variant in ZMYM2 in two different families with CAKUT.

COL4A1 mutations as a potential novel cause of autosomal dominant CAKUT in humans.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease (~ 45%) that manifests before 30 years of age. The genetic locus containing COL4A1 (13q33-34) has been implicated in vesicoureteral reflux (VUR), but mutations in COL4A1 have not been reported in CAKUT. We hypothesized that COL4A1 mutations cause CAKUT in humans.

Effect of angiotensin converting enzyme gene I/D polymorphism in South Indian children with nephrotic syndrome.

Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%-15% of nephrotic syndrome cases are non-responders of steroid treatment (SRNS).

Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tract.

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most prevalent cause of kidney disease in the first three decades of life. Previous gene panel studies showed monogenic causation in up to 12% of patients with CAKUT.

Methods: We applied whole-exome sequencing to analyze the genotypes of individuals from 232 families with CAKUT, evaluating for mutations in single genes known to cause human CAKUT and genes known to cause CAKUT in mice.

A homozygous missense variant in VWA2, encoding an interactor of the Fraser-complex, in a patient with vesicoureteral reflux.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause (40-50%) of chronic kidney disease (CKD) in children. About 40 monogenic causes of CAKUT have so far been discovered. To date less than 20% of CAKUT cases can be explained by mutations in these 40 genes.

Wilms' tumour 1 gene mutations in south Indian children with steroid-resistant nephrotic syndrome.

Background & Objectives: Clinically, nephrotic syndrome (NS) is a diverse group of symptoms; about 20 per cent of NS cases are resistant to steroid treatment, and within ten years they progress to end-stage renal disease. The present study was undertaken to identify the mutations of Wilms' tumour 1 (WT1) gene in steroid-resistant NS (SRNS) children.

Methods: A total of 173 children with SRNS and 100 children in the control group were enrolled in the study.

WT1 and NPHS2 gene mutation analysis and clinical management of steroid-resistant nephrotic syndrome.

Nephrotic syndrome (NS) is a kidney disease predominantly present in children with idiopathic condition; final stage of the disease progresses into end-stage renal disease. Generally, NS is treated using standard steroid therapy, however; most of the children are steroid sensitive and about 15-20% are non-responders (SRNS). Non-responsiveness of these children would be a risk with the possibility of mutational changes in podocyte genes (NPHS1, NPHS2, WT1, PLCE1).

Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract.

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined.

Budding adult hypertensives with modifiable risk factors: "Catch them young".

Background: Since the data of primary hypertension (HT) in children is scanty in India, this study attempted to evaluate HT by a multidimensional investigation of the various risk factors in children and adolescents.

Materials And Methods: A total of 3906 subjects were recruited, all of whom lived in Chennai, an urban area of Tamil Nadu. The children and adolescents aged from 10 to 17 years were selected by random sampling.

Association of HLA-DR/DQ alleles and haplotypes with nephrotic syndrome.

Background: Nephrotic syndrome (NS) is a debilitating renal problem in children resulting from an interaction between environmental and genetic factors including human leukocyte antigen genes (HLA). The aim of this work was to study the probable link between HLA alleles/haplotypes and NS in south India.

Methods: HLA DRB1*/DQB1* alleles were genotyped in 183 NS (76 steroid sensitive-SSNS; 107 steroid resistant-SRNS) and paediatric healthy controls (PHCs; n = 91) using polymerase chain reaction-sequence specific primers (PCR-SSP).

gene promoter polymorphisms in steroid resistant nephrotic syndrome children.

Nephrotic syndrome (NS) is the most frequent cause of proteinuria in children and is emerging as a leading cause of uremia. Among idiopathic NS, 10% of children do not respond to steroids or to any other immunosuppressive therapy, and progress to end-stage renal disease (ESRD). Several studies have investigated the mutations in genes encoding podocyte proteins and their possible associations with several forms of hereditary NS.

Efficacy and safety of valsartan in hypertensive children 6 months to 5 years of age.

Objective: To evaluate a dose-dependent reduction in blood pressure (BP) and overall safety of valsartan in hypertensive children.

Method: In a multicenter, randomized, double-blind, parallel-group study, 75 patients with a documented history of hypertension were randomized (2 : 1 : 2) to receive valsartan (0.25, 1 or 4  mg/kg per day) for 6 weeks, then rerandomized (1 : 1) to receive placebo or valsartan for 2 weeks.

Management of steroid sensitive nephrotic syndrome: revised guidelines.

Justification: In 2001, the Indian Pediatric Nephrology Group formulated guidelines for management of patients with steroid sensitive nephrotic syndrome. In view of emerging scientific evidence, it was felt necessary to review the existing recommendations.

Process: Following a preliminary meeting in March 2007, a draft statement was prepared and circulated among pediatric nephrologists in the country to arrive at a consensus on the evaluation and management of these patients.

Twins with senior-Loken syndrome.

Senior-Loken syndrome is a rare entity that combines familial juvenile nephronophthisis with retinal dystrophy. The eye disease may be congenital amaurosis of Leber type or pigmentary retinal degeneration and electroretinogram (ERG) helps in the diagnosis of these varieties. The disease progresses inexorably to chronic renal failure.