scholarly journals The podocin V260E mutation predicts steroid resistant nephrotic syndrome in black South African children with focal segmental glomerulosclerosis

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Melanie A. Govender ◽  
June Fabian ◽  
Errol Gottlich ◽  
Cecil Levy ◽  
Glenda Moonsamy ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
South African ◽  
Focal Segmental Glomerulosclerosis ◽  
Steroid Resistance ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Black South African ◽  
African Children ◽  
Segmental Glomerulosclerosis ◽  
South African Children

AbstractIn black African children with focal segmental glomerulosclerosis (FSGS) there are high rates of steroid resistance. The aim was to determine genetic associations with apolipoprotein L1 (APOL1) renal risk variants and podocin (NPHS2) variants in 30 unrelated black South African children with FSGS. Three APOL1 variants were genotyped and the exons of the NPHS2 gene sequenced in the cases and controls. APOL1 risk alleles show a modest association with steroid sensitive nephrotic syndrome (SSNS) and steroid resistant nephrotic syndrome (SRNS). The NPHS2 V260E variant was present in SRNS cases (V/V = 5; V/E = 4; E/E = 11), and was absent in SSNS cases. Haplotype analysis suggests a single mutation origin for V260E and it was associated with a decline in kidney function over a 60-month period (p = 0.026). The V260E variant is a good predictor of autosomal recessive SRNS in black South African children and could provide useful information in a clinical setting.

scholarly journals NPHS2 V260E Is a Frequent Cause of Steroid-Resistant Nephrotic Syndrome in Black South African Children

2018 ◽  
Vol 3 (6) ◽  
pp. 1354-1362 ◽  
Author(s):  
Kareshma Asharam ◽  
Rajendra Bhimma ◽  
Victor A. David ◽  
Hoosen M. Coovadia ◽  
Wenkosi P. Qulu ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
South African ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Black South African ◽  
African Children ◽  
South African Children

APOL1 risk genotype in European steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis patients of different African ancestries

2018 ◽  
Vol 34 (11) ◽  
pp. 1885-1893 ◽  
Author(s):  
Olivier Gribouval ◽  
Olivia Boyer ◽  
Bertrand Knebelmann ◽  
Alexandre Karras ◽  
Jacques Dantal ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
West Indies ◽  
African Ancestry ◽  
Compound Heterozygous ◽  
French West Indies ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Segmental Glomerulosclerosis ◽  
Risk Variants

Abstract Background Apolipoprotein L1 (APOL1) risk variants are strongly associated with sporadic focal segmental glomerulosclerosis (FSGS) in populations with African ancestry. We determined the frequency of G1/G2 variants in steroid-resistant nephrotic syndrome (SRNS)/FSGS patients with African or French West Indies ancestry in France and its relationships with other SRNS genes. Methods In a cohort of 152 patients (139 families), the APOL1 risk variants were genotyped by direct Sanger sequencing and pathogenic mutations were screened by next-generation sequencing with a panel including 35 SRNS genes. Results The two risk allele [high-risk (HR)] genotypes were found in 43.1% (66/152) of subjects compared with 18.9% (106/562) in a control population (P < 0.0001): 33 patients homozygous for APOL1 G1 alleles, 4 homozygous for G2 and 29 compound heterozygous for G1 and G2. Compared with patients in the low-risk (LR) group, patients in the HR group were more likely to originate from the French West Indies than from Africa [45/66 (68.2%) versus 30/86 (34.9%); P < 0.0001]. There were more familial cases in the HR group [27 (41.5%) versus 8 (11.4%); P < 0.0001]. However, causative mutations in monogenic SRNS genes were found in only 1 patient in the HR group compared with 16 patients (14 families) in the LR group (P = 0.0006). At diagnosis, patients in the HR group without other mutations were more often adults [35 (53.8%) versus 19 (27.1%); P = 0.003] and had a lower estimated glomerular filtration rate (78.9 versus 98.8 mL/min/1.73 m2; P = 0.02). Conclusions The HR genotype is frequent in FSGS patients with African ancestry in our cohort, especially in those originating from the West Indies, and confer a poor renal prognosis. It is usually not associated with other causative mutations in monogenic SRNS genes.

scholarly journals Genetic Study in Korean Pediatric Patients with Steroid-Resistant Nephrotic Syndrome or Focal Segmental Glomerulosclerosis

2020 ◽  
Vol 9 (6) ◽  
pp. 2013
Author(s):  
Eujin Park ◽  
Chung Lee ◽  
Nayoung K. D. Kim ◽  
Yo Han Ahn ◽  
Young Seo Park ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Detection Rate ◽  
Pediatric Patients ◽  
Mutation Detection ◽  
Genetic Diagnosis ◽  
Mutation Detection Rate ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Segmental Glomerulosclerosis

Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes of end-stage renal disease (ESRD) in childhood and is mostly associated with focal segmental glomerulosclerosis (FSGS). More than 50 monogenic causes of SRNS or FSGS have been identified. Recently, the mutation detection rate in pediatric patients with SRNS has been reported to be approximately 30%. In this study, genotype-phenotype correlations in a cohort of 291 Korean pediatric patients with SRNS/FSGS were analyzed. The overall mutation detection rate was 43.6% (127 of 291 patients). WT1 was the most common causative gene (23.6%), followed by COQ6 (9.4%), NPHS1 (8.7%), NUP107 (7.1%), and COQ8B (6.3%). Mutations in COQ6, NUP107, and COQ8B were more frequently detected, and mutations in NPHS2 were less commonly detected in this cohort than in study cohorts from Western countries. The mutation detection rate was higher in patients with congenital onset, those who presented with proteinuria or chronic kidney disease/ESRD, and those who did not receive steroid treatment. Genetic diagnosis in patients with SRNS provides not only definitive diagnosis but also valuable information for decisions on treatment policy and prediction of prognosis. Therefore, further genotype-phenotype correlation studies are required.

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