Podocyte-associated gene mutation screening in a heterogeneous cohort of patients with sporadic focal segmental glomerulosclerosis

Laurin, Louis Philippe; Lu, Mengji; Mottl, Amy K.; Blyth, Elizabeth R.; Poulton, Caroline J.; Weck, Karen E.

doi:10.1093/ndt/gft532

Cited by 29 publications

(16 citation statements)

References 49 publications

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“…Consistently, a recent study that analyzed genetic mutations in children affected by sporadic FSGS without considering the response to treatment found a frequency of potentially pathogenic mutations of about 10%. 27 Our study also has some limitations. Indeed, it is a retrospective study that analyzed all patients with sporadic nephrotic syndrome who were referred to our hospital and gave informed consent to the study.…”

Section: Discussionmentioning

confidence: 87%

Heterogeneous Genetic Alterations in Sporadic Nephrotic Syndrome Associate with Resistance to Immunosuppression

Giglio

Provenzano²,

Mazzinghi

et al. 2015

Journal of the American Society of Nephrology

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In children, sporadic nephrotic syndrome can be related to a genetic cause, but to what extent genetic alterations associate with resistance to immunosuppression is unknown. In this study, we designed a custom array for next-generation sequencing analysis of 19 target genes, reported as possible causes of nephrotic syndrome, in a cohort of 31 children affected by sporadic steroid-resistant nephrotic syndrome and 38 patients who exhibited a similar but steroid-sensitive clinical phenotype. Patients who exhibited extrarenal symptoms, had a familial history of the disease or consanguinity, or had a congenital onset were excluded. We identified a genetic cause in 32.3% of the children with steroid-resistant disease but zero of 38 children with steroid-sensitive disease. Genetic alterations also associated with lack of response to immunosuppressive agents in children with steroid-resistant disease (0% of patients with alterations versus 57.9% of patients without alterations responded to immunosuppressive agents), whereas clinical features, age at onset, and pathologic findings were similar in steroid-resistant patients with and without alterations. These results suggest that heterogeneous genetic alterations in children with sporadic forms of nephrotic syndrome associate with resistance to steroids as well as immunosuppressive treatments. In these patients, a comprehensive screening using such an array may, thus, be useful for genetic counseling and may help clinical decision making in a fast and cost-efficient manner.

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Section: Discussionmentioning

confidence: 87%

Heterogeneous Genetic Alterations in Sporadic Nephrotic Syndrome Associate with Resistance to Immunosuppression

Giglio

Provenzano²,

Mazzinghi

et al. 2015

Journal of the American Society of Nephrology

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“…Mutations in these genes, however, explain only a small fraction of familial and sporadic FSGS cases (8)(9)(10). A larger fraction of cases may involve nonFocal segmental glomerulosclerosis (FSGS) is a syndrome that involves kidney podocyte dysfunction and causes chronic kidney disease.…”

Section: Introductionmentioning

confidence: 99%

A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis

Yu¹,

Artomov²,

Brähler³

et al. 2016

Journal of Clinical Investigation

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“…The APOL1 G1 and G2 risk alleles in the African American population with FSGS is significantly enriched as compared to the general population. HRM will be an ideal technique to rapidly screen for these alleles in our population [42]. …”

Section: Discussionmentioning

confidence: 99%

Screening of WT1 mutations in exon 8 and 9 in children with steroid resistant nephrotic syndrome from a single centre and establishment of a rapid screening assay using high-resolution melting analysis in a clinical setting

et al. 2017

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BackgroundMutations in Wilm’s tumor 1 (WT1) gene is one of the commonly reported genetic mutations in children with steroid resistant nephrotic syndrome (SRNS). We report the results of direct sequencing of exons 8 and 9 of WT1 gene in 100 children with SRNS from a single centre. We standardized and validated High Resolution Melt (HRM) as a rapid and cost effective screening step to identify individuals with normal sequence and distinguish it from those with a potential mutation. Since only mutation positive samples identified by HRM will be further processed for sequencing it will help in reducing the sequencing burden and speed up the screening process.MethodsOne hundred SRNS children were screened for WT1 mutations in Exon 8 and 9 using Sanger sequencing. HRM assay was standardized and validated by performing analysis for exon 8 and 9 on 3 healthy control and 5 abnormal variants created by site directed mutagenesis and verified by sequencing. To further test the clinical applicability of the assay, we screened additional 91 samples for HRM testing and performed a blinded assessment.Results WT1 mutations were not observed in the cohort of children with SRNS. The results of HRM analysis were concordant with the sequencing results.ConclusionThe WT1 gene mutations were not observed in the SRNS cohort indicating it has a low prevalence. We propose applying this simple, rapid and cost effective assay using HRM technique as the first step for screening the WT1 gene hot spot region in a clinical setting.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-016-0362-7) contains supplementary material, which is available to authorized users.

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Podocyte-associated gene mutation screening in a heterogeneous cohort of patients with sporadic focal segmental glomerulosclerosis

Cited by 29 publications

References 49 publications

Heterogeneous Genetic Alterations in Sporadic Nephrotic Syndrome Associate with Resistance to Immunosuppression

Heterogeneous Genetic Alterations in Sporadic Nephrotic Syndrome Associate with Resistance to Immunosuppression

A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis

Screening of WT1 mutations in exon 8 and 9 in children with steroid resistant nephrotic syndrome from a single centre and establishment of a rapid screening assay using high-resolution melting analysis in a clinical setting

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