Related Experiment Video
Updated: Jun 30, 2026
06:39
Glomerular Outgrowth as an Ex Vivo Assay to Analyze Pathways Involved in Parietal Epithelial Cell Activation
Published on: August 19, 2020
NPHS2 variation in focal and segmental glomerulosclerosis
Stephen J Tonna1, Alexander Needham, Krishna Polu
1Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. stonna@rics.bwh.harvard.edu
BMC Nephrology
|October 1, 2008
Summary
Mutations in the NPHS2 gene are a rare cause of focal and segmental glomerulosclerosis (FSGS) in adults. Common NPHS2 variants do not increase proteinuria risk in the general population or associate with kidney dysfunction in diabetics.
Area of Science:
- Nephrology
- Genetics
- Molecular Biology
Background:
- Focal and segmental glomerulosclerosis (FSGS) is a primary cause of proteinuria in adults.
- Mutations in the podocin gene (NPHS2) are implicated in pediatric steroid-resistant nephrotic syndrome and FSGS.
Purpose of the Study:
- To investigate the spectrum of genetic variations in the NPHS2 gene in adults with late-onset FSGS.
- To determine the frequency and clinical significance of NPHS2 mutations in adult FSGS.
Main Methods:
- DNA analysis of 371 individuals with predominantly late-onset FSGS.
- Sequencing of the NPHS2 gene to identify non-synonymous alleles.
- Genotyping of common NPHS2 variants in the Nurses' Health Study and diabetic cohorts.
Main Results:
- Fifteen non-synonymous NPHS2 alleles were identified in 17% of subjects, including 7 novel variants.
- 3.2% of individuals had homozygous or compound heterozygous NPHS2 mutations.
- Common variants p.A242V and p.R229Q did not increase albuminuria risk or associate with diabetic nephropathy.
Conclusions:
- NPHS2 mutations are infrequent causes of FSGS in the adult population.
- The most common NPHS2 variants do not appear to be significant risk factors for proteinuria or kidney dysfunction in the general or diabetic populations.
- This study clarifies the prevalence of NPHS2 mutations in adult FSGS and expands the understanding of NPHS2-related kidney diseases.
Related Concept Videos
01:24Nephrotic Syndrome I : Introduction
Nephrotic Syndrome is a chronic kidney disorder defined by clinical findings such as severe proteinuria, hypoalbuminemia, hyperlipidemia, and edema. These symptoms result from damage to the glomeruli, the kidney’s filtering units, increasing their permeability to proteins.Definition and Meaning:Proteinuria, defined as the loss of more than 3.5 grams of protein per day in adults, is a crucial feature of nephrotic syndrome. This condition is often accompanied by edema, the accumulation of fluid...
02:26Comparing Copy Number Variations and SNPs
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
01:10Nephrons
The kidneys are intricate organs with millions of working units known as nephrons. Each nephron features two major structures: the renal corpuscle, which facilitates blood plasma filtration, and the renal tubule, which handles the glomerular filtrate. Blood supply is directly linked to the nephrons. The renal corpuscle consists of the glomerulus, a capillary network, and the Bowman's capsule, a double-walled epithelial structure that encases the glomerulus. The filtering of blood plasma happens...
01:05Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
01:26Nephrotic Syndrome II : Assessment and Medical Management
IntroductionNephrotic syndrome is a kidney disorder marked by excessive protein loss in the urine, leading to various systemic complications. This condition often results from damage to the glomeruli—the kidney's filtering units—causing proteinuria, low blood protein levels, and fluid retention. Understanding the assessment, diagnosis, and management of nephrotic syndrome is essential for effective treatment and prevention of further kidney damage.AssessmentPatient History: Document any history...
01:28Diabetic Nephropathy
Definition Diabetic nephropathy is a chronic kidney complication that results from prolonged hyperglycemia.Prevalence It is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, affecting up to half of individuals with diabetes.Pathophysiology • Sustained hyperglycemia triggers multiple hemodynamic and metabolic changes in the kidney. • Early in the disease, increased renal blood flow and glomerular hyperfiltration occur due to afferent arteriolar...