Exclusion of homozygous PLCE1 (NPHS3) mutations in 69 families with idiopathic and hereditary FSGS

Abstract

Focal and segmental glomerulosclerosis (FSGS) is the most common glomerular cause of endstage kidney disease (ESKD). 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 were recently 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.Results-A total of 69 families with 231 affected individuals were examined. The median age of disease onset was 26 years (range 1-66). Onset of ESKD was a median of 35.5 years. Seven variants leading to non-synonymous changes were found, of these, only two were new variants (exon4 c.1682 G>A R561Q, exon31 c.6518A>G K2173R). No known disease-causing mutations were identified in the families screened.Conclusion-PLCE1/NPHS3 mutations are not a cause of FSGS in this cohort. 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 genomewide screening will be subjected to analysis to identify other genetic causes of FSGS.

R229Q Polymorphism of NPHS2 Gene in Group of Iraqi Children with Steroid-Resistant Nephrotic Syndrome

“…This is similar to many other studies from different regions [11–16]. Consanguinity was found in high percentage in both groups, which is expected in this community because of social traditions.…”

Genetic variation in PLCE1 is associated with gastric cancer survival in a Chinese population

“…Previous research on PLCE1 has mainly focused on its impact in diseases of the urinary system, including nephrotic syndrome (NS), focal and segmental glomerulosclerosis (FSGS), and diffuse mesangial sclerosis (DMS) [24][25][26][27].…”

PLCE1 rs2274223 Polymorphism and Susceptibility to Esophageal Cancer: a Meta-analysis

“…The rs2274223 locates in the 26 exon and causes histidine transfer to arginine (Ma et al, 2011;Zhou et al, 2011;Yu et al, 2013). It has been a hot topic to study the relationship between PLCE1 rs2274223 gene polymorphism and susceptibility to head and neck cancer and the relationship between PLCE1 rs2274223 gene polymorphism and susceptibility to esophageal cancer has caused wide public concern (Gbadegesin et al, 2009;Ma et al, 2011;Abnut et al, 2012;Mai et al, 2012;Cui et al, 2014).…”