Screening of the LAMB2, WT1, NPHS1, and NPHS2 Genes in Pediatric Nephrotic Syndrome

Mutations in the NPHS1, NPHS2, LAMB2, and the WT1 genes are responsible for causing nephrotic syndrome (NS) in two third of the early onset cases. This study was carried out to assess the frequencies of mutations in these genes in a cohort of pediatric NS patients. A total of 64 pediatric familial or sporadic SRNS cases were recruited. Among these, 74% had a disease onset of up to 3 years of age. We found one homozygous frameshift mutation in the NPHS1 gene in one CNS case and two homozygous mutations in the NPHS2 gene. Six mutations in four cases in the LAMB2 gene were also identified. No mutation was detected in the WT1 gene in isolated SRNS cases. LAMB2 gene missense mutations were segregating in NS cases with no extra-renal abnormalities. Analysis of the population genomic data (1000 genome and gnomAD databases) for the prevalence estimation revealed that NS is more prevalent than previously determined from clinical cohorts especially in Asian population compared with overall world populations (prevalence worldwide was 1in 189036 and in South-Asian was 1in 56689). Our results reiterated a low prevalence of mutations in the NPHS1, NPHS2, LAMB2, and WT1 genes in the studied population from Pakistan as compared to some European population that showed a high prevalence of mutations in these genes. This is a comprehensive screening of the genes causing early onset NS in sporadic and familial NS cases suggesting a more systematic and robust approach for mutation identification in all the 45 disease-causing genes in NS in our population is required

Impact of Immunofluorescence on the Histological Pattern of Pediatric Kidney Biopsies from Northern Pakistan

Kidney biopsy is an investigation for diagnosis and prognosis of a variety of nephritides. It also influences therapeutic options. Immunofluorescence (IMF) greatly adds in identifying the pathologies which may not be obvious on light microscopy (L/M), such as IgM, IgA nephropathy, pauci-immune glomerulonephritis, and anti-glomerular basement membrane disease. We present here data of 170 pediatric kidney biopsies from July 2005 to December 2009 from Department of Nephrology and Hypertension, Lady Reading Hospital, Peshawar, Pakistan. The study was undertaken to see whether IMF would alter the histological pattern of pediatric kidney biopsies and to compare these data with an earlier data from our department of 415 pediatric kidney biopsies done over 7-year period from 1998 to 2005, which were analyzed with L/M alone. Out of 170 kidney biopsies using L/M and IMF, IgM turns out to be most common pattern (20%%), followed by minimal change disease (MCD) (17.05%%), focal and segmental glomerulosclerosis (FSGS) (15.88%%), chronic sclerosing glomerulonephritis (Chr. sclerosing GN) (12.35%%), mesangio proliferative glomerulonephritis (MPGN) (7.65%%), mesangio capillary glomerulonephritis (MCGN) (6.47%%), membranous glomerulonephritis (Mem. GN) (5.29%%), IgA nephropathy (5.29%%), cresentic glomerulonephritis (Cres. GN) (3.53%%), lupus nephritis (2.96%%), and others (3.53%%). Comparing these results of 170 cases with 415 renal biopsies without IMF, IgM dominated the histological pattern in IMF group whereas MCD followed by FSGS and MPGN were prominent in group without IMF. Therefore, variation in the overall histological pattern with IMF technique proved statistically significant (p \u3c 0.0001). Addition of IMF has altered the frequency of MCD, a change from 24%% (100/415) to 17%% (29/170), FSGS from 18.3%% (76/415) to 15.88%% (27/170), and MPGN from 17.35%% (72/415) to 7.65%% (13/170)