Table 3:
Information on pre-NGS histological diagnosis and post-NGS genetic diagnosis in the 39 patients in whom a pathogenic variant was identified.
| Fa m ID |
ID | Se x |
Fam Hx |
Age at Bx |
Histological Diagnosis |
Cr. at biopsy (umols/L) |
Fibrosis on Bx (%) |
Genetic Dx | Chr position |
c. change p. change |
Zygosity | MAF | ACMG | Type |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TIKD | ||||||||||||||
| 2 | 2A | M | Yes | 38 | TIKD/ gouty nephropathy | 232 | 50 | UMOD | 16 | c.G767G>A p.Cys256Tyr | Het | 0 | Likely path. | Non- Synonymous SNV |
| 2 | 2B | F | Yes | 22 | TI fibrosis | - | 50 | UMOD | 16 | c.G767G>A p.Cys256Tyr | Het | 0 | Likely path. | Non-Synonymous SNV |
| 2 | 2C | M | Yes | 18 | TI fibrosis | 201 | 65 | UMOD | 16 | c.G767G>A p.Cys256Tyr | Het | 0 | Likely path. | Non-Synonymous SNV |
| 3 | 3A | F | Yes | 47 | Familial TIKD | - | 80 | MUC1 | 1 | c. ins(3n+1) in VNTR p. MUC1fs | Het | - | Path. | Frameshift Insertion |
| 3 | 3B | F | Yes | 38 | Familial TIKD | - | 70 | MUC1 | 1 | c. ins(3n+1) in VNTR p. MUC1fs | Het | - | Path. | Frameshift Insertion |
| 3 | 3C | F | Yes | 43 | Active TI Nephritis | 150 | 75 | MUC1 | 1 | c. ins(3n+1) in VNTR p. MUC1fs | Het | - | Path. | Frameshift Insertion |
| 3 | 3D | M | Yes | 42 | Familial TIKD | 140 | 70 | MUC1 | 1 | c. ins(3n+1) in VNTR p. MUC1fs | Het | - | Path. | Frameshift Insertion |
| 3 | 3E | M | Yes | 46 | Familial TIKD | 177 | 75 | MUC1 | 1 | c. ins(3n+1) in VNTR p. MUC1fs | Het | - | Path. | Frameshift Insertion |
| 3 | 3F | F | Yes | 53 | TI fibrosis | - | 10 | MUC1 | 1 | c. ins(3n+1) in VNTR p. MUC1fs | Het | - | Path. | Frameshift Insertion |
| 4 | 4 A* | F | Yes | 38 | Early TI fibrosis | 146 | - | HNF1B | 17 | c.544+3_544+ 6del / | Het | 0 | Path. | Deletion |
| 5 | 5A * | F | Yes | 19 | TI Inflammation | 1355 | 50 | NPHP1 | 17 | c.555_556insA p.Pro186Hisfs* 2 | Hom | 0 | Path. | Non-synonymous SNV |
| 6 | 6 A* | M | Yes | 26 | Early Nephronophthisis | 46 | <10 | IFT140 | 16 | c.634G>A p.Gly212Arg | Hom | 5.4×10−5 | Path. | Non-Synonymous SNV |
| 15 | 15 A | F | Yes | 54 | TIKD | 638 | 50 | UMOD | 16 | c.317G>A p.Cys106Tyr | Het | 0 | Path. | Non-synonymous SNV |
| Glomerulonephritis | ||||||||||||||
| 2 | 2D | M | Yes | 52 | MPGN | 101 | 20 | UMOD | 16 | c.G767G>A p.Cys256Tyr | Het | 0 | Likely path. | Non-Synonymous SNV |
| 7 | 7A | F | Yes | 55 | Proliferative GN | 67 | 10 | MUC1 | 1 | c.ins(3n+1) in VNTR p. MUC1fs | Het | - | Path. | Frameshift Insertion |
| 8 | 8A | M | Yes | 65 | IgA GN | 90 | 30 | COL4A5 | X | c.2959_2976del p.987_992del | Het | 0 | Likely path. | Non-frameshift deletion |
| 9 | 9A | M | Yes | 41 | Focal proliferative GN | 80 | <10 | COL4A5 | X | c.3427G>Ap.Gly1143Ser | Hemi | 0 | Likely path. | Non-synonymous SNV |
| Focal Segmental Glomerulosclerosis/ Alport Syndrome | ||||||||||||||
| 11 | 11A* | M | Yes | 20 | FSGS | 1350 | 80 | COL4A5 | X | c.2605G>Ap.Gly869Arg | Hemi | 0 | Path. | Non-Synonymous SNV |
| 12 | 12A* | F | Yes | 33 | Alport Syndrome | 100 | 10 | COL4A5 | X | c.2396G>Ap.Gly799Asp | Het | 0 | Likely path. | Non- Synonymous SNV |
| 13 | 13A* | M | Yes | 24 | Alport Syndrome | 170 | 10 | COL4A5 | X | c.1423+1G>T | Hemi | 0 | Path. | Essential Splice Site |
| 14 | 14A* | M | No | 13 | FSGS | 165 | >50 | FANCI | 15 | c.217A>Tp.Ile73Phe | Hom | 1.4×10−5 | Likely path. | Non-Synonymous SNV |
| 16 | 16A | M | Yes | 34 | Alport Syndrome | 169 | 10 | COL4A5 | X | c. 1762G>Ap.Gly588Ser | Hem | 0 | Likely path. | Non-Synonymous SNV |
| 17 | 17A | M | Yes | 20 | Alport Syndrome | 72 | 30−55 | COL4A5 | X | c.3310G>Tp.Gly1104Cys | Hem | 0 | Likely path. | Non-synonymous SNV |
| Thrombotic Microangiopathy | ||||||||||||||
| 4 | 4B* | M | Yes | 43 | Chronic TMA | 135 | 20 | HNF1B | 17 | c.544+3_544+6del / | Het | 0 | Likely Path. | Deletion |
| 6 | 6B* | F | Yes | 11 | TMA & TBMN | 301 | 60–70 | IFT140 | 16 | c.634G>Ap.Gly212Arg | Hom | 5.4×10−5 | Path. | Non-Synonymous SNV |
| 15 | 15B | M | Yes | 44 | Chronic TMA/ FSGS | 400 | 75 | UMOD | 16 | c.317G>Ap.Cys106Tyr | Het | 0 | Path | Non-synonymous SNV |
| 15 | 15C | M | Yes | 42 | Chronic TMA | 133 | 30 | UMOD | 16 | c.317G>Ap.Cys106Tyr | Het | 0 | Path. | Non-synonymous SNV |
| 18 | 18A | M | Yes | 24 | TMA & TBMN | 99 | 40 | INF2 | 14 | c.640C>Tp.Arg214Cys | Het | 4.08×10–6 | Likely path | Non-synonymous SNV |
| 18 | 18B | F | Yes | 23 | TMA & TBMN | 75 | 50 | INF2 | 14 | c.640C>Tp.Arg214Cys | Het | 4.08×10–6 | Likely path. | Non-synonymous SNV |
| 18 | 18C | M | Yes | 28 | TMA & TBMN | 94 | 20 | INF2 | 14 | c. 640 C>Tp.Arg214Cys | Het | 4.08×10–06 | Likely path. | Non-synonymous SNV |
| 18 | 18D | M | Yes | 34 | TMA & TBMN | 154 | 60 | INF2 | 14 | c.640C>Tp.Arg214Cys | Het | 4.08×10–6 | Likely path. | Non-synonymous SNV |
| 19 | 19A | M | Yes | 30 | TMA & TBMN | 106 | 20 | MUC1 | 1 | c. ins(3n+1) in VNTRp. MUC1fs | Het | - | Path. | Frameshift Insertion |
| 20 | 20A | F | Yes | 42 | Acute TMA | - | 15 | HNF1B | 17:36064929 | c.1255_1256del p.Ala419fs | Het | 0 | Likely path. | Frameshift deletion |
| Non-Specific Changes | ||||||||||||||
| 20 | 20B | M | Yes | 42 | Oligomeganephro nia | 167 | 75 | HNF1B | 17 | c.1255_1256del p.Ala419fs | Het | 0 | Likely path. | Frameshift deletion |
| 8 | 8B | M | Yes | 56 | Arteriosclerosis with fibrosis | 225 | 70 | COL4A5 | X | c.2959_2976del p.987_992del | Hem | 0 | Likely path. | Non-frameshift deletion |
| 21 | 21A* | M | Yes | 18 | Within normal limits | 60 | 0 | C3 | 19 | c.4534C>Tp.Arg1512Cys | Het | 8.12×10–6 | Likely path. | Non-Synonymous SNV |
| 21 | 21B* | F | Yes | 20 | Mesangialproliferation | 170 | 60–70 | INF2 | 14 | c.353T>Ap.Ile118Asn | Het | 0 | Path. | Non-Synonymous SNV |
| 22 | 22A* | F | Yes | 32 | Arteriosclerosis | 62 | 5 | WNK4 | 17 | c.506C>Tp.Pro169Leu | Het | 0 | Path. | Non-Synonymous SNV |
| 23 | 23A* | M | No | 25 | Severe fibrosis | 191 | >70 | SLC3A1 | 2 | c.1799G>Ap.Gly600Glu | Het | 7×10−5 | Likely Path. | Non-Synonymous SNV |
A, adenine; ACMG, American College of Medical Genetics; AD, autosomal dominant; AR, autosomal recessive; Bx, Biopsy; c. Change, nucleotide change; C, cytosine; Chr, Chromosome; Cr, creatinine; DDD, dense deposit disease; del, deleterious; D.M, disease mutation; Dx, diagnosis; ESS, essential splice site; F, Female; Fam Hx, Family History; Fam ID, family identity number; FS, Frame Shift; FSGS, Focal Segmental Glomerulosclerosis; fs, frameshift mutation; G, guanine; GN, Glomerulonephritis; hem, hemizygous; het, heterozygous; hom, homozygous; ID, personal identity number; IG, immunoglobulin; M, male; MAF; Minor Allele frequency; p. Change, amino acid change; Path, pathogenic; PKD, polycystic kidney disease; SNV, single nucleotide variation; T, thymine; TI, Tubulointerstitial; TBMN, Thin Basement Membrane Nephropathy; TIKD, tubulointerstitial kidney disease; TMA, thrombotic microangiopathy;
Genetic diagnosis as reported by Connaughton DM, Kennedy C, Shril S, et al. Monogenic causes of chronic kidney disease in adults. Kidney Int. February 2019. doi:10.1016/j.kint.2018.10.03