Table 2.
Five probands in whom early genetic diagnosis could have affected clinical care
| Family | Gene | Gender, Ethnicity | Age at Presentation/Age at ESRD | Clinical Details | Biopsy (if done) | Retrospective or Prospective Implications after WES |
|---|---|---|---|---|---|---|
| B2404 | AGXT | Female, Indian | 2 mo/2.5 mo | • Presented with advanced CKD in infancy | None | • Early initiation of daily hemodialysis to decrease risk for systemic oxalosis |
| • Initial work-up included normal serum oxalate level | • Earlier listing for combined liver-kidney transplantation | |||||
| • Presumed diagnosis of renal dysplasia | ||||||
| • PH1 diagnosis made at 1 yr of age during evaluation for LRD transplant | ||||||
| B188 | NPHS2 | Female, white | 3 yr/12 yr | • Presented with edema, proteinuria, and hypoalbuminemia | FSGS | • Avoidance of pretransplant IS and pheresis catheter placement |
| • Treatment with steroids, cyclophosphamide, cyclosporine, and ACE inhibitors | • Using a lower-risk (e.g., steroid minimization) protocol for IS given low risk for recurrence | |||||
| • Received plasmapheresis before transplantation to reduce risk of FSGS recurrence8,39-41 | ||||||
| B354 | PLCE1 | Male, Pakistani | 12 mo/15 mo | • Presented with edema and proteinuria | Biopsy 1: mesangial proliferative GN | • Avoidance of pretransplant IS (steroids and cyclosporine) |
| • No response to steroids or calcineurin inhibitors | Biopsy 2: DMS | |||||
| B2559 | TRPC6 | Female, white | 11 yr/11 yr | • Presented with malignant hypertension, anemia, thrombocytopenia, and elevated LDH | Global and segmental sclerosis, tubular atrophy, interstitial fibrosis | • No need for treatment with eculizumab |
| • Received treatment with eculizumab because of concern for atypical HUS and initiated on hemodialysis | • Genetic counseling given autosomal dominant inheritance and 50% risk of passing along mutant allele | |||||
| B92 | WT1 | Female, white | 4 yr/13 yr | • Treatment with steroids, cyclophosphamide, and ACE inhibitors | FSGS | • Earlier initiation of hormone therapy and prophylactic gonadectomy |
| • Gonadal dysgenesis diagnosed at 18 yr of age during work-up for primary amenorrhea |
LRD, living related donor; ACE, angiotensin-converting enzyme; IS, immunosuppression; DMS, diffuse mesangial sclerosis; LDH, lactate dehydrogenase; HUS, hemolytic uremic syndrome.