Table 1.
Overview of identified variants.
| Family (origin) | Gene (NM_number) | Chromosomal position (hg19) | Nucleotide change, amino acid change, and corresponding ClinVar and/or LOVD ID | Inheritance | gnomADa MAF | ACMG ratingb | Biopsy (initial clinical presentation) | Affected (gender) | Positive familial history | Consanguinity | Individual ages (years) | CKD-stage (age in years) | Present inclusion criteriac | Previously published | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Disease onset | ESRD | ||||||||||||||
| F9 (GE) | COL4A3 (NM_000091.4) | NC_000002.11: g.[228144508G>C]; [228172594T>C] | c.[2126-1G>C];[4421T>C], p.[?];[Leu1474Pro] LOVD ID: 0000665278; ClinVar ID: SCV001149720.1 | AR | Not listed; 2.66e−3 | PVS1/PM2, PS4 (moderate, in trans with pathogenic variant)/ PM1/PM3/PP3 | FSGS (NS) | 1 (m) | No | No | 26 | – | G3aA3 (30) | 1 | No; [42, 43] |
| F274 (GE) | COL4A5 (NM_000495.3) | NC_000023.10: g.[107850086G>A]; [=] | c.[2359G>A];[=], p.[Gly787Arg];[=] ClinVar ID: SCV001150068.1 | XL | Not listed | PS2/PM1 (strong)/PM2/PM5/PP3 | Focal segmental and global GS (hypertension) | 1 (f) | No | No | 32.5 | – | G3aA3 (40) | 1, 3 | No |
| F26 (TU) | COQ8B (NM_024876.4) | NC_000019.9: g.[41198128C>A]; [41198128C>A] | c.1447G>T(;)(1447G>T), p.Glu483*(;)(Glu483*) ClinVar ID: SCV001149996.1 | AR | 5.16e−5 (no homozygotes present) | PVS1/PS4 (moderate)/ PM2 | FSGS (proteinuria) | 2 (m, f) | Yes | Yes | 24, 32 | 24, – | G5-D (24), G2A3 (32) | 1, 5, 6 | [38] |
| F103 (GE) | INF2 (NM_022489.3) | NC_000014.8: g.[105169540G>C]; [=] | c.[490G>C];[=], p.[Ala164Pro];[=] LOVD ID: 0000665276 | AD | Not listed | PM1/PM2/PP1 (strong)/PP3/ | Minimal change disease, mesangioprol. GN IgA type (proteinuria, hypertension) | 10 (m, m, f, f, f, m, m, m, m, m) | Yes | No | 18, 19, 24, 25, 18, 32, 32, 19, 31, 26 | 30, 39, –, –, 38, 38, –, –, –, – | G5-D (30), G5-D (39), G1A? (39), G2A? (35), G5-D (38), G5-D (38), n.k., G4A3 (38), G3bA3 (32), G2A3 (27) | 1, 2, 5 | [44] |
| F27 (GE) | INF2 (NM_022489.3) | NC_000014.8: g.[105169653C>T]; [=] | c.[529C>T];[=], p.[Arg177Cys];[=] ClinVar ID: SCV001149810.1 | AD | Not listed | PS4 (moderate)/PM1/PM2/PP3 | IgA/Immune complex nephritis, FSGSd (proteinuria) | 1 (m) | No | No | 18 | – | G4A3 (37) | 2 | [45] |
| F332 (GE) | MUC1 (NM_001204285.1) | NC_0000001.10: g.(155160963_155162030)insC | c.(103_564)insG;[=], p.[?];[=] LOVD ID: 0000673664 | AD | Not listed | PS3/PS4 (moderate)/PM2 | Focal global GS (creatinine increase) | 1 (m) | Yes | No | 32 | 41 | G5-D (41) | 1, 5 | [26] |
| F520 (RO) | WT1 (NM_024426.4) | NC_000011.9: g.[32413514G>A]; [=] | c.[1432+4C>T];[=], p.[?];[=] LOVD ID: 0000673826 | AD | Not listed | PS3/PS4 (moderate)/PM2/PP3 | FSGS (edema) | 1 (m [f])e | No | No | 18 | 18 | G5-D (18) | 1, 2, 4 | [46] |
P pathogenic, PP pathogenic supporting, VS very strong, S strong, M moderate, A? albuminuria unknown, AR autosomal recessive, AD autosomal dominant, ClinVar ID https://www.ncbi.nlm.nih.gov/clinvar/, CKD V-D chronic kidney disease stadium V-dialysis, XL X-linked, ESRD end-stage renal disease, FSGS focal segmental glomerulosclerosis, GE Germany, LOVD ID https://databases.lovd.nl/shared, MAF minor allele frequency, NS nephrotic syndrome, n.k. not known, – not applicable, RO Romania, TU Turkey.
aGenome Aggregation Database (https://gnomad.broadinstitute.org/).
cInclusion criteria: 1: absence of a secondary cause for FSGS; 2: age ≤ 25 years at initial manifestation; 3: kidney biopsy with suspicion of a hereditary cause; 4: extrarenal manifestation; 5: positive familial history; and 6: reported consanguinity.
dInitial biopsy IgA/immunocomplex nephritis, second biopsy 7 years later FSGS.
eGenetic sex is a male karyotype (46,XY), the phenotype is female with unfulfilled desire to have children.