Table 5.
Phenotypes of patients with pathogenic variants in 1 of 23 genes that if mutated cause nephrotic syndrome after multiplex PCR and NGS in 362 families (371 patients) with proteinuria and hematuria with an age of onset <25 years
| Family | Sex | Age of onset (ESRD) | Proteinuria | Hematuria | Biopsy | Family history | Ethnicity (consanguinity) | Extrarenal treatment (response) | Biobase |
|---|---|---|---|---|---|---|---|---|---|
| ACTN4 | |||||||||
| A1055 | M | 10 years | UPC 4 mg/mg | Y, type N/A | FSGS | None | Kurd (Y) | SS(CR), CS(CR) | Novel |
| ARHGDIA | |||||||||
| A1432 | F | 2 years (3 years) | ACR 0.85 mg/mg | Y, type N/A | DMS | None | Jewish (Y) | DF, SST, ID, CS(NR), TX | [42] |
| M | 1 year (1 year) | 17.3 g/day | Y, type N/A | ND | None | Jewish (Y) | SST, TX | [42] | |
| COQ2 | |||||||||
| A103 | F | 1 year | 4 g/day | Y, type N/A | FSGS | None | Euro (N) | SR, CS(PR) | [16, 43] |
| CUBN | |||||||||
| A1213 | M | 12 | ACR 0.28 mg/mg | Microscopic | ND | None | Balkan (N) | Hypocalcemia | [44] |
| M | 5 years | ACR 0.26 mg/mg | Microscopic | ND | None | Balkan (N) | − | [44] | |
| M | <1× month | ACR 0.9 mg/mg | Microscopic | ND | None | Balkan (N) | − | [44] | |
| INF2 | |||||||||
| A675 | F | 16 years | UPC 7.5 mg/mg | Y, type N/A | FSGS | None | Euro (N) | Steroids(UR) | [45]a |
| LAMB2 | |||||||||
| A1757 | M | 13 years | 2.8 g/day | Y, type N/A | FSGS | Aunt | Hisp (N) | HTN, SR, Cellcept(NR) | Novel |
| F | 13 years | Y | Y, type N/A | FSGS | Aunt | Hisp (N) | − | Novel | |
| A2356 | M | 1 year | 4+ | Microscopic | Finnish type | 2 Brothers | Asian (Y) | Blindness | [16, 46] |
| A1613 | M | <1 month | 9.8 g/day | Y, type N/A | Dilated tubules, Microcysts | None | Euro (N) | FTT | [16, 47] |
| LMX1B | |||||||||
| A200 | F | 8 years (9 years) | 1.5 g/day | Y, type N/A | FSGS | Mother | Turk (Y) | SR, HemDi | [16, 48] |
| A2175 | M | 4 years (43 years) | 3.1 g/L | Y, N/A | FSGS | None | Euro (N) | Factor XII Deficiency, SR, CS(PR), Acei(UR), HemDi, TX | [16, 48] |
| A3180 | F | 18 years (43 years) | UPC 2 mg/mg | Y, type N/A | FSGS | None | Euro (N) | HemDi, TX | [16, 48] |
| A4009 | F | <1 month | UPC 4 mg/mg | Y, type N/A | MCNS | None | Arabic (Y) | SR, CS(NR) | Novela |
| NPHS1 | |||||||||
| A1803 | M | <1 month | UPC 38 mg/mg | Microscopic | MCNS | None | Cauc (N) | CS(NR) | Novela |
| A3775 | F | 1 year | 0.95 g/day | Y, type N/A | Diffuse MesP | None | Indian (N) | SS(CR) | [49]a |
| A3380 | M | <1 month | Y | Y, type N/A | ND | None | Asian (N) | − | [50, 51] |
| B115 | F | <1 month | 50 mg/mg | Y, type N/A | ND | None | Cauc (N) | Hypothyroidism | [52] |
| A1500 | F | 1 year | UPC 20 mg/mg | Y, type N/A | MCNS | None | Afr-Am (N) | HTN | [53, 54] |
| NPHS2 | |||||||||
| A4681 | F | 7 years | UPC 8 mg/mg | Y, type N/A | FSGS | None | Arabic (Y) | SR | [16] |
| A4624 | F | 1 year | UPC 3.9 mg/mg | Y, type N/A | MPGN | None | Arabic (Y) | HTN, SR, CP(NR), CS(NR) | [17, 51, 55, 56] |
| B188 | F | 3 years (15 years) | 3+ | Macroscopic | MCNS | None | Hisp (Y) | TX | [57, 58]a |
| A1616 | F | 5 months | 2.2 g/day | Y, type N/A | ND | None | Cauc (N) | Presentation post infection | [59–61] |
| A2239 | M | <18 | 5.1 g/day | Microscopic | FSGS | Cousin | Turk (N) | − | [62]a |
| PLCE1 | |||||||||
| A3233 | F | 2 | UPC 8.4 mg/mg | Y, type N/A | ND | None | Arabic (Y) | HTN, SR, CP(NR) | [16] |
| A3617 | F | 7 months | UPC 12 mg/mg | Y, type N/A | FSGS | Cousin, aunt | Arabic (Y) | − | [16] |
| A3510 | F | 1 year | UPC 2.7 mg/mg | Microscopic | ND | None | Turk (Y) | HTN | [16] |
| A3869 | M | 7 months | UPC 4.5 mg/mg | Y, type N/A | FSGS | None | Arabic (Y) | − | [16] |
| SMARCAL1 | |||||||||
| A3146 | F | 9 years | 5 g/day | Y, type N/A | FSGS | None | Euro (N) | HTN, ID | [63]a |
| A4162 | F | 4 years | UPC 7.5 mg/mg | Y, type N/A | FSGS | None | Euro (N) | Celiac, VSD, PDA, SR, CS(UR) | [16] |
| TRPC6 | |||||||||
| A4685 | F | 17 years | UPC 9.8 mg/mg | Y, type N/A | FSGS | None | Arabic (N) | HTN, Allergies, CS(NR) | [17] |
The genes sequenced were ACTN4, ADCK4, ARHGAP24, ARHGDIA, CD2AP, COQ2, COQ6, CUBN, INF2, ITGA3, ITGB4, LAMB2, LMX1B, MYO1E, NPHS1, NPHS2, PDSS2, PLCE1, PTPRO, SMARCAL1, TRPC6 and WT1.
Solved in this study using multiplex PCR.
ACEi, angiotensin-converting enzyme inhibitor; ACR, albumin:creatinine ratio; Afr-Am, African American; Cauc, Caucasian; CP, cyclophosphamide; CR, complete response; CS, cyclosporine; DF, deafness; DMS, diffuse mesangial sclerosis; Euro, European; F, female; FSGS, focal segmental glomerulosclerosis; FTT, failure to thrive; HemDi, hemodialysis; Hisp, Hispanic; HTN, hypertension; ID, intellectual disability; M, male; MCNS, minimal change nephrotic syndrome; MesP, mesangial proliferation; MPGN, membrane proliferative glomerulonephritis; N, no; ND, not done; NR, no response; PDA, persistent ductus arteriosus; PR, partial response; SR, steroid resistant; SS, steroid sensitive; SST, short stature; Turkish; TX, transplant; type N/A, hematuria type unknown; UPC, urine protein:creatinine ratio; UR, unknown response; VSD, ventricular septal defect; Y, yes.