NPHS1 and NPHS2 Gene Mutations in Chinese Children With Sporadic Nephrotic Syndrome

Mao, Jianhua; Zhang, Yang; Du, Lizhong; Dai, Yuwen; Gu, Wei; Liu, Ai'Min; Shang, Shiqiang; Liang, Li

doi:10.1203/01.pdr.0000250041.19306.3d

Cited by 36 publications

(26 citation statements)

References 25 publications

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“…The lack of NPHS2 mutations in this cohort of AA children with SRNS is in contrast with previous studies indicating a rate of 10.5-28% mutations in large cohorts of pediatric SRNS [19][20][21]. However, our findings add to the growing evidence that ethnic difference exists in the rate of NPHS2 mutations, as not all ethnic groups share the same frequency of mutations in this gene [14,[19][20][21][22][23][24][25][26][27][28][29][30][31]. These differences emphasize the need for further NPHS2 mutation analysis of other ethnic groups in which the frequency of NPHS2 mutations is still unknown.…”

Section: Discussioncontrasting

confidence: 91%

“…In Israeli Arab children with familial and sporadic SRNS, an NPHS2 mutation rate of 55% was found, which is higher than reported in worldwide cohorts [22]. Two separate Turkish cohorts of SRNS patients found an NPHS2 mutation rate of 27.4% [23] and 13.3% [24], and a Chinese study found a mutation rate of 15.9%, similar to the findings in worldwide cohorts [25]. On the other hand, a lower 4% prevalence of NPHS2 mutation rate was found in a different Chinese cohort [26] and in one out of 13 Japanese children with congenital NS [27].…”

Section: Introductionsupporting

confidence: 74%

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Low prevalence of NPHS2 mutations in African American children with steroid-resistant nephrotic syndrome

et al. 2008

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In African American (AA) children, focal segmental glomerulosclerosis (FSGS) is the leading cause of nephrotic syndrome (NS). It has been shown that AA children suffer from FSGS and steroid-resistant nephrotic syndrome (SRNS) at a higher frequency and with a more severe renal outcome in comparison with Caucasian children. Previous mutation analysis of large cohorts revealed that a high percentage of childhood SRNS is monogenic and that mutations in podocin (NPHS2) and Wilms' tumor gene 1 (WT1) account for approximately 30% of SRNS in children. To test whether AA children with SRNS have a similar or a higher mutation rate, we performed mutation analysis of NPHS2 and WT1 in a cohort of AA children with SRNS. Direct sequencing was carried out for all exons of NPHS2 and for exons 8 and 9 of WT1. We ascertained 18 children of AA descent in whom renal biopsy findings showed FSGS in 13 patients (72%) and minimal-change disease in five patients (28%). In both NPHS2 and WT1, no disease-causing mutations were detected. Our data strongly suggest that in AA children with SRNS, the frequency of NPHS2 mutations is much lower than in large cohorts of pediatric SRNS patients in the general population. Knowledge of mutation rate of NPHS2 in different populations of SRNS patients facilitates the physician in planning a suitable genetic screening strategy for patients.

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Section: Discussioncontrasting

confidence: 91%

Section: Introductionsupporting

confidence: 74%

Low prevalence of NPHS2 mutations in African American children with steroid-resistant nephrotic syndrome

et al. 2008

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“…Thus, we speculate that the deterioration of renal function might be accelerated by two mutations of NPHS2 and WT1 genes. Di-genic heterozygosity has been reported in some patients, including NPHS2 combined with NPHS1 or CD2AP mutations, and a mutation in NPHS1 combined with a WT1 mutation (19,20). Our study, for the first time, demonstrated the di-genic heterozygosity of NPHS2 mutation combined with a WT1 mutation might exist in Chinese patients with NS.…”

Section: Discussionsupporting

confidence: 56%

WT1 Gene Mutations in Chinese Children With Early Onset Nephrotic Syndrome

Ding

Zhao

et al. 2010

Pediatr Res

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ABSTRACT:In Chinese children with steroid-resistant nephrotic syndrome (SRNS), it was reported that NPHS2 mutation was detected in 4.3%, which was lower than that in Caucasians (10 -30%). However, there were no data on WT1 mutation in nephrotic syndrome (NS), especially in early-onset NS of Chinese children. Thus, a study, which enrolled 36 Chinese children with early-onset (before 3 y old) NS and steroid resistance if failing steroid therapy (early-group), was conducted. As control, 35 children with SRNS and with disease onset age after 3 y old were also analyzed (control-group). WT1 gene was examined by PCR and direct sequencing. The result showed that in the early-group 6/36 (16.7%) were detected with WT1 mutations. Further analysis according to different onset age revealed that the mutation detection rates of WT1 were 26.3% (5/19), 6.3% (1/16), and 0 (0/1) in children younger than 1 y, 1-2 y, and 2-3 y, respectively. In control-group, no WT1 (0/35) mutation was detected. WT1 mutation combined with NPHS2 variant was detected in a girl. In conclusion, WT1 mutations seemed more common in Chinese children with early-onset NS. (Pediatr Res 68: 155-158, 2010) N ephrotic syndrome (NS) is often a life-threatening condition when manifesting as early-onset, especially in the first year of life. In recent years, several causative genes related to NS have been identified by applying molecular genetic approaches, including NPHS1, NPHS2, WT1, LAMB2, PLCE1, ACTN4, TRPC6,. These genes have been analyzed in a large cohort of patients with NS worldwide, especially NPHS1, NPHS2, and WT1. The results suggested that, in these genes, NPHS1 mutations were mainly detected in children with congenital NS (CNS), and WT1 and NPHS2 might be more common in children with primary steroid-resistant nephrotic syndrome (SRNS) (9 -11). As to WT1 gene, previous studies by other groups revealed that the incidence of WT1 mutations in isolated SRNS children (6.8 y in average age) was 6 -7% (9,10), and the two hot spots were exons 8 and 9 in WT1 gene. Nevertheless, there were few reports on the incidence of WT1 mutations in children with early-onset NS, especially in the first year of life. In China, there are numerous children with early-onset NS for whom neither the incidence nor clinical characteristics of WT1 gene mutations are clear. The identification of gene mutations associated with early-onset NS will definitely help Chinese childhood patients to obtain the correct diagnosis, to prevent excessive drug therapy, and to obtain the suitable genetic consultation. Therefore, we detected WT1 mutations in a large cohort of children with early-onset NS and analyzed the phenotypic characterization in children with WT1 mutations. METHODS Patients.A total of 36 unrelated children of Chinese ethnicity with early-onset NS (within 3 y, early-group) was enrolled in this study. There were 30/36 children in the early-group who received steroid therapy (1.5-2 mg/kg daily for 8 wk) and presented with steroid resistance. The other 6/36 cases had not received ...

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“…However, outside of Finland, the NPHS1 mutation detection rate is 39-80% in cases with CNS (Lenkkeri et al, 1999;Hinkes et al, 2007;Heeringa et al, 2008;Ismaili et al, 2009;Schoeb et al, 2010). Currently, only 8 NPHS1 mutations have been described in Chinese individuals, including 1 deletion (c.1983-1900del8) (Shi et al, 2005), 1 insertion (c.3250insG) (Yu et al, 2012), 1 nonsense mutation (c.2783C>A) (Wu et al, 2011), and 5 missense mutations (D310N, Q453R, I742T, R800C, V957L) (Shi et al, 2005;Mao et al, 2007;Wu et al, 2011). In this study, we found a novel splice-site mutation (IVS11+1G>A) in NPHS1 that caused CNS in a Chinese child.…”

Section: Discussionmentioning

confidence: 99%

Novel NPHS1 splice site mutations in a Chinese child with congenital nephrotic syndrome

Fu¹,

Gou²,

Ma³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Congenital nephrotic syndrome (CNS) is defined as heavy proteinuria or nephrotic syndrome occurring before 3 months of age. It is characterized by early onset and progresses to end-stage renal disease. Recently, several genes associated with CNS have been identified, including NPHS1 and NPHS2. Mutations in the NPHS1 gene have been identified in patients with CNS in Finland with relatively high frequency. Thus far, only a few case reports about CNS have described an NPHS1 mutation in China. In this study, mutational analyses of NPHS1 and NPHS2 were performed in a Chinese child with CNS. Mutations were analyzed in all exons and exon/intron boundaries of NPHS1 and NPHS2 in the patient and his parents as well as in 50 unrelated controls using polymerase chain reaction and A novel splice site mutation (IVS11+1G>A) within intron 11 and a missense mutation within exon 8 (c.928G>A) in the NPHS1 gene were detected in the child. The child's mother had normal urinalysis and a c.928G>A (D310N) heterozygous mutation, and his father had normal urinalysis and IVS11+1G>A. These were not identified in the 50 unrelated controls. The novel splice site mutation of IVS11+1G>A and a missense mutation at c.928G>A in NPHS1 were found to cause CNS in this Chinese child.

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NPHS1 and NPHS2 Gene Mutations in Chinese Children With Sporadic Nephrotic Syndrome

Cited by 36 publications

References 25 publications

Low prevalence of NPHS2 mutations in African American children with steroid-resistant nephrotic syndrome

Low prevalence of NPHS2 mutations in African American children with steroid-resistant nephrotic syndrome

WT1 Gene Mutations in Chinese Children With Early Onset Nephrotic Syndrome

Novel NPHS1 splice site mutations in a Chinese child with congenital nephrotic syndrome

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