Table 2.
Summary of the results of whole-exome sequencing and reverse phenotyping in phenocopy patients
| Patient | Sex | Ethnicity | Pre Whole-Exome Sequencing Diagnosis/Biopsy Results | Gene | Variant | Reverse Phenotyping Diagnosis | Post Whole-Exome Sequencing Diagnosis | Phenotype OMIM Number (#) |
|---|---|---|---|---|---|---|---|---|
| Case 1 | F | Senegalese | SRNS/FSGS | COL4A4 APOL1 | Hom Comp het | - SNHL not present at onset and diagnosed by rechecking WES results | Alport syndrome | 203780 |
| - Father with mild proteinuria and microscopic hematuria | ||||||||
| - Mother with microscopic hematuria | ||||||||
| Confirmed Alport syndrome | ||||||||
| Case 2 | F | European | SRNS/FSGS | COL4A4 | Comp het | - Parents with microscopic hematuria | Alport syndrome | 203780 |
| Confirmed Alport syndrome | ||||||||
| Case 3 | F | European | SRNS/MCD | COL4A3 | Comp het | - Parents with microscopic hematuria | Alport syndrome | 203780 |
| Confirmed Alport syndrome | ||||||||
| Case 4 | F | European | SRNS/FSGS | COL4A5 | Het | - Mother affected by SNHL | Alport syndrome | 301050 |
| Confirmed Alport syndrome | ||||||||
| Case 5 | M | European | SRNS/MCD | COL4A5 | Hem | - SNHL not present at onset and diagnosed by rechecking WES results | Alport syndrome | 301050 |
| - Mother with microscopic hematuria | ||||||||
| Confirmed Alport syndrome | ||||||||
| Case 6 | F | European | SRNS/FSGS | COL4A5 | Het | - Mother developed nephrotic syndrome during pregnancy (regressed after delivery) | Alport syndrome | 301050 |
| Confirmed Alport syndrome | ||||||||
| Case 7 | M | European | SRNS/FSGS | LAMB2 | Comp het | - Sister with chronic glomerulopathy of unknown etiology | Pierson syndrome | 609049 |
| Confirmed Pierson syndrome | ||||||||
| Case 8 | F | European | SRNS/FSGS | GLA | Het | - Podocyte vacuolization and microscopic lamellar bodies on EM | Fabry disease | 301500 |
| - Father affected by SNHL | ||||||||
| Confirmed Fabry disease | ||||||||
| Case 9 | M | European | SRNS/FSGS | FAT1 | Hom | - Cluster headache | FAT1-related glomerulotubular nephropathy | — |
| - Tubular atrophy | ||||||||
| Confirmed FAT1-related glomerulotubular nephropathy | ||||||||
| Case 10 | F | European | SRNS/- | FAT4 | Comp het | - Left kidney hypodysplasia at kidney scintigraphy (normal US scanning) | Van Maldergem syndrome 2 | 615546 |
| Confirmed kidney involvement in Van Maldergem syndrome 2 | ||||||||
| Case 11 | F | European | SRNS/FSGS | PAX2 | Het | - No ocular abnormalities | Papillo-renal syndrome/FSGS | 120330 |
| Confirmed FSGS in Papillo-renal syndrome | ||||||||
| Case 12 | F | Latino | SRNS/- | PAX2 | Het | - No ocular abnormalities | Papillo-renal syndrome/FSGS | 120330 |
| Confirmed FSGS in Papillo-renal syndrome | ||||||||
| Case 13 | M | European | SRNS/FSGS | CLCN5 | Hem | - Growth failure | Dent disease | 300009 |
| Confirmed Dent disease | ||||||||
| Case 14 | M | European | SRNS/MCD | CLCN5 | Hem | - Late-onset hypercalciuria | Dent disease | 300009 |
| Confirmed Dent disease | ||||||||
| Case 15 | M | European | SRNS/FSGS | CLCN5 | Hem | - Microlithiasis | Dent disease | 300009 |
| Confirmed Dent disease | ||||||||
| Case 16 | M | European | SRNS/MCD | CTNS | Comp het | - Corneal crystals at slit-lamp examination | Cystinosis | 219800 |
| - Multinucleated podocytes on EM on kidney biopsy | ||||||||
| - Intraleukocytes cystin levels 2 nmol/mg protein (normal <0.3) | ||||||||
| Confirmed cystinosis | ||||||||
| Case 17 | M | Tunisian | SRNS/FSGS | LMX1B | Het | - Lack of ossification nuclei of the radium (bilateral) | Nail-patella syndrome | 161200 |
| - Severe growth failure | ||||||||
| - Absence of thumbs lunulae | ||||||||
| - Father with microscopic hematuria and mild proteinuria | ||||||||
| Confirmed Nail-patella syndrome | ||||||||
| Case 18 | M | European | SRNS/MCD | KANK1 | Comp het | - Multidrug resistant epilepsy | Cerebral palsy | 612900 |
| Confirmed cerebral palsy |
All postwhole-exome sequencing diagnoses are defined according to OMIM nomenclature (https://www.omim.org) with the exception of FAT1-related glomerulotubular nephropathy (37). OMIM, Online Mendelian Inheritance in Man; F, female; SRNS, steroid-resistant nephrotic syndrome; Hom, homozygous; Comp het, compound heterozygous; SNHL, sensorineural hearing loss; MCD, minimal change disease; Het, heterozygous; M, male; Hem, hemizygous; WES, whole-exome sequencing; EM, electron microscopy; -, biopsy not performed; US, ultrasound.