Article Figures & Data
Figures
- Figure 1.
Geographic distribution of the study cohort of 1783 families with SRNS. The number of affected families in the respective countries or cities is represented by the surface area (red) of a circle. Data from countries not represented on the map are shown in the blue box. Insert shows higher resolution of the New York Metropolitan area.
- Figure 2.
Age of onset distribution (in years) for 1589 of 1783 examined SRNS families. The displayed 1589 families represent the number of families with available data for age of onset of proteinuria <18 years. (A) Red curve and histograms represent the number of families in each age of onset (years) of SRNS for 1093 families without molecular genetic diagnosis. Blue curve and histograms show number of 496 families with causative mutations identified for each age of onset. (B) Graph indicates percentage of solved families per year of age of onset (from A). Black dotted line represents a binomial fit of age-related percent of families with causative mutation. (Data are not displayed for 72 individuals who were older than 17 years at onset of SRNS and for 122 families with no available information for age of onset. In families with >1 affected family member, the mean age of onset from all affected individuals was used.)
- Figure 3.
Detection of the causative mutation in 502 families in an international cohort of 1617 families with SRNS in 21 SRNS-causing genes in relation to age of onset of proteinuria in clinically relevant age groups. The displayed 502 families represent the number of families with detected causative mutation and available data for age of onset of proteinuria <26 years. (A) Percentage of families with causative mutation detected per gene per age group. Histograms indicate fraction (in percentage) of families with causative gene detected in n families per families examined (on top of histograms) per age group. (B) Percentages shown in A are represented by separate bars to highlight distribution across age groups as further delineated in C. Note that mutations in NPHS1 or LAMB2 cause early-onset SRNS, whereas mutations in INF2 or TRPC6 cause late-onset SRNS. (C) Percentages of families with causative mutation detected (from B) are interconnected by lines between age groups and shown in different colors for each causative gene (lower panel for recessive genes, upper panel for dominant genes). NPHS1 mutations (red) have an early age of onset and are rarely found in patients older than 6 years. The dominant genes INF2 and TRPC6 manifest in early adulthood and WT1 (black) shows a biphasic distribution (upper panel). (For families with detected disease-causing mutation, data are not shown for 11 families where no age of onset was available, and for 10 families with an age of onset older than 25 years. For families with no detection of the disease-causing mutation, data are not displayed for 111 families for whom no data for age of onset were available and for 34 families with age of onset older than 25 years. In families with >1 affected family member the mean age of onset from all affected individuals was calculated.).
- Figure 4.
Distribution for age of onset of NS in 35 individuals with homozygous mutations in PLCE1. (A) Homozygous PLCE1 mutations are represented by 30 different alleles. The x-axis indicates the mutations sorted by median age of onset. The y-axis indicates the age of onset of SRNS. Symbols are colored red, green, or blue if the allele is truncating, splice, or missense, respectively. (B) Age of onset of SRNS with causative mutations detected in PLCE1, grouped by type of mutation. The x-axis indicates the type of mutations (truncating mutations before amino acid (aa) residue 1000 (N-terminal), truncating mutations after aa residue 1000 (C-terminal), splice and missense mutations. The y-axis indicates the age of onset of proteinuria. Symbols are blue for missense, green for splice, and red for stop and frameshift. Note that the age of onset was significantly different between splice site mutations versus C-terminal truncating mutations (P<0.05), or splice site versus missense mutations (P<0.05). P values are from two-tailed t test. Arrows represent position of outlier values.
Tables
- Table 1.
International cohort of 526 of the 1783 families, in whom a single-gene cause of SRNS was detected in 1 of 21 monogenic causes of SRNS (27 genes examined)
Gene Causing SRNS Mode of Inheritance SRNS Families Molecularly Diagnosed by Sanger Sequencing (Published Previously), na SRNS Families Molecularly Diagnosed by Multiplex PCR (n) Total SRNS Families with Molecular Diagnosis (% of Families) NPHS2 AR 170 (42) 7 177 (9.93) NPHS1 AR 93 (61) 38 131 (7.34) WT1 AD 78 (50) 7 85 (4.77) PLCE1 AR 23 (16) 14 37 (2.17) LAMB2 AR 10 (6) 10 20 (1.12) SMARCAL1 AR 1 (0) 15 16 (0.89) INF2 AD 2 (0) 7 9 (0.5) TRPC6 AD 1 (1) 8 9 (0.53) COQ6 AR 6 (5) 2 8 (0.45) ITGA3 AR 3 (3) 2 5 (0.28) MYO1E AR 0 (0) 5 5 (0.28) CUBN AR 1 (1) 4 5 (0.28) COQ2 AR 0 (0) 4 4 (0.22) LMX1B AD 0 (0) 4 4 (0.22) ADCK4 AR 3 (3) 0 3 (0.17) DGKE1 AR 0 (0) 2 2 (0.11) PDSS2 AR 0 (0) 2 2 (0.11) ARHGAP24 AD 0 (0) 1 1 (0.06) ARHGDIA AR 1 (1) 0 1 (0.06) CFH AR 0 (0) 1 1 (0.06) ITGB4 AR 0 (0) 1 1 (0.06) Total 392 (189) 134 526 (29.5) AD, autosomal dominant; AR, autosomal recessive.
↵a Number in parenthesis show “molecularly solved” families with causative mutation detected that were published before from our cohort (see literature).
Supplemental Data
Files in this Data Supplement:
In this issue
Jump to section
More in this TOC Section
Cited By...
- Contributions of Rare Gene Variants to Familial and Sporadic FSGS
- A Bigenic mouse model of FSGS reveals perturbed pathways in podocytes, mesangial cells and endothelial cells
- Molecular genetic analysis of Steroid Resistant Nephrotic Syndrome: Detection of a novel mutation
- Evaluating Mendelian nephrotic syndrome genes for evidence of risk alleles or oligogenicity that explain heritability
- Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients
- Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tract
- Strong Association of the HLA-DR/DQ Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese Population
- Clinical syndromes associated with Coenzyme Q10 deficiency
- Whole Exome Sequencing Reveals a Monogenic Cause of Disease in {approx}43% of 35 Families With Midaortic Syndrome
- Endoplasmic reticulum-retained podocin mutants are massively degraded by the proteasome
- Need to Reclassify Etiologies of ESRD on the CMS 2728 Medical Evidence Report
- Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach
- Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome
- Clinical genetic testing using a custom-designed steroid-resistant nephrotic syndrome gene panel: analysis and recommendations
- Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children
- New Insights into Podocyte Biology in Glomerular Health and Disease
- MAGI2 Mutations Cause Congenital Nephrotic Syndrome
- Modeling Monogenic Human Nephrotic Syndrome in the Drosophila Garland Cell Nephrocyte
- Focal Segmental Glomerulosclerosis
- PLC{varepsilon}1 regulates SDF-1{alpha}-induced lymphocyte adhesion and migration to sites of inflammation
- Minimal Change Disease
- Recurrent FSGS Postkidney Transplant: Moving the Needle Forward
- Using Population Genetics to Interrogate the Monogenic Nephrotic Syndrome Diagnosis in a Case Cohort
- Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid-Resistant Nephrotic Syndrome