Table 5.
Revision of Electron Microscopy Images by a Kidney Pathologist of 7 patients With a Mono-allelic COL4A3 or COL4A4 Variant and Blind Comparison With 14 Controls
| Patient ID | Sex (M/F) | Age at Kidney Biopsy (y) | GBM Thickness (μm) Median (Range) |
Total Number Available EM Images | Total Number Points in GBM Measured (n) | GBM Thickness: Consistency | Podocyte Foot Effacement | Endothelial Swelling/Injury | Clinical and Genetic Findings |
|---|---|---|---|---|---|---|---|---|---|
| Patients with a mono-allelic COL4A3/COL4A4 variant | |||||||||
| Index 2 | F | 38 | 0.23 (0.14-0.35) | 6 | 25 | Variable | + | + | Mono-allelic COL4A3 variant c.2083G>A (p.Gly695Arg) |
| Index 3 | M | 55 | 0.31 (0.1-0.55) | 5 | 47 | Variable | + | + | Mono-allelic COL4A3 variant c.2083G>A (p.Gly695Arg) |
| Index 4 | M | 52 | 0.28 (0.13-0.42) | 6 | 25 | Variable | + | ++ | Mono-allelic COL4A3 variant c.2801G>A (p.Gly934Glu) |
| Index 8 | F | 65 | 0.42 (0.27-0.65) | 3 | 20 | Variable | + | + | Mono-allelic COL4A4 variant c.1571G>A (p.Gly524Glu) |
| Index 9 | F | 43 | 0.26 (0.13-0.46) | 7 | 34 | Variable | + | + | Mono-allelic COL4A3 variant c.2690G>A (p.Gly897Glu) |
| Index 16 | F | 45 | 0.22 (0.14-0.34) | 4 | 24 | Variable | + | + | Mono-allelic COL4A4 variant c.3532G>A (p.Gly1178Ser) |
| Index 17 | M | 56 | 0.31 (0.18-0.47) | 5 | 43 | Variable | + | + | Mono-allelic COL4A4 variant c.3706G>A (p.Gly1236Arg) |
| Controls | |||||||||
| 1 | M | 36 | 0.49 (0.15-0.71) | 5 | 15 | Variable | ++ | - | iFSGS |
| 2 | M | 59 | 0.33 (0.2-0.64) | 6 | 16 | Variable | ++ | ++ | iFSGS |
| 3 | M | 42 | 0.34 (0.17-0.77) | 6 | 22 | Highly variable | ++ | ++ | iFSGS |
| 4 | M | 85 | 0.44 (0.3-0.61) | 5 | 24 | Variable | ++ | + | iFSGS |
| 5 | M | 50 | 0.36 (0.23-0.47) | 5 | 21 | Low variability | ++ | - | iFSGS |
| 6 | M | 23 | 0.48 (0.25-0.91) | 7 | 31 | Variable | ++ | + | iFSGS |
| 7 | M | 65 | 0.31 (0.17-0.48) | 7 | 34 | Variable | + | + | SRNS |
| 8 | M | 36 | 0.35 (0.21-0.66) | 5 | 28 | Variable | ++ | - | SRNS |
| 9 | F | 43 | 0.22 (0.13-0.37) | 6 | 39 | Variable | + | + | SRNS |
| 10 | M | 28 | 0.38 (0.27-0.63) | 6 | 40 | Variable | ++ | + | SRNS |
| 11 | M | 17 | 0.37 (0.36-0.8) | 1 | 3 | Low variability | + | - | SRNS Mono-allelic NPHS2 variant c.686G>A (p.Arg229Gln)a |
| 12 | F | 51 | 0.31 (0.14-0.7) | 6 | 24 | Variable | ++ | + | Compound heterozygous NPHS2 variants c.686G>A (p.Arg229Gln) and c.862G>A (p.Ala288Thr) |
| 13 | F | 18 | 0.63 (0.4-0.79) | 3 | 5 | Consistent | ++ | + | Compound heterozygous CRB2 variants c.3313C>T (p.Arg1105Cys) and c.3846_3849del (p.Glu1282fs) Mono-allelic NPHS1 variant c.3549C>A (p.Tyr1183∗) |
| 14 | F | 2 | 0.32 (0.23-0.42) | 2 | 10 | Low variability | ++ | + | Compound heterozygous COQ2 variants c.590G>A (p.Arg197His) and c.683A>G (p.Asn228Ser) |
Note: Controls included 14 kidney biopsies: patients with a different hereditary nephropathy diagnosed by whole exome sequencing (WES) in our center (n = 3); patients with a steroid resistant nephrotic syndrome (SRNS) (kidney gene panel by WES negative for a disease-causing DNA variants) (n = 5); and patients with idiopathic FSGS (iFSGS) with a complete or partial remission on prednisone (no genetic test performed) (n = 6). Podocyte effacement was classified as none (-), ≤80% (+), or >80% (++). Endothelial injury was classified as none (-), moderate (+), or severe (++).
Abbreviations: EM, electron microscopy; F, female; GBM, glomerular basement membrane; iFSGS, idiopathic focal segmental glomerulosclerosis; M, male; SRNS, steroid resistant nephrotic syndrome.
Reference sequence used are: NPHS2 NM_014625.3, CRB2 NM_173689.6, NPHS1 NM_004646.3, COQ2: NM_015697.7, COL4A3 NM_000091.4, COL4A3 NM_000092.4.