Exclusion of homozygous PLCE1 (NPHS3) mutations in 69 families with idiopathic and hereditary FSGS.
Focal and segmental glomerulosclerosis (FSGS) is the most common glomerular cause of end-stage kidney disease (ESKD). Although the etiology of FSGS has not been fully elucidated, recent results from the positional cloning of genes mutated in nephrotic syndromes are now beginning to provide insight into the pathogenesis of these diseases. Mutations in PLCE1/NPHS3 have recently been reported as a cause of nephrotic syndrome characterized by diffuse mesangial sclerosis (DMS) histology. One single family with a missense mutation had late onset of the disease that was characterized by FSGS. To further define the role of PLCE1 mutations in the etiology of FSGS, we performed mutational analysis in 69 families with FSGS. A total of 69 families with 231 affected individuals were examined. The median age of disease onset was 26 years (range 1-66 years). Onset of ESKD was at a median age of 35.5 years. Seven variants leading to non-synonymous changes were found, of which only two are new variants (exon 4 c.1682 G>A R561Q, exon 31 c.6518A>G K2173R). No known disease-causing mutations were identified in the families screened. PLCE1/NPHS3 mutations are not a cause of FSGS in this cohort. The absence of mutations in PLCE1/NPHS3 in this study indicates that there are additional genetic causes of FSGS and that hereditary FSGS is a heterogeneous disease. Kindreds appropriate for genome-wide screening are currently being subjected to analysis with the aim of identifying other genetic causes of FSGS.
Duke Scholars
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- Young Adult
- Urology & Nephrology
- Polymorphism, Single Nucleotide
- Phosphoinositide Phospholipase C
- Mutation, Missense
- Middle Aged
- Humans
- Homozygote
- Glomerulosclerosis, Focal Segmental
- Family Health
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Young Adult
- Urology & Nephrology
- Polymorphism, Single Nucleotide
- Phosphoinositide Phospholipase C
- Mutation, Missense
- Middle Aged
- Humans
- Homozygote
- Glomerulosclerosis, Focal Segmental
- Family Health