Table 3.
Pathogenic variants in non-COL4A genes
| Patient ID (Family ID) | Sex | Ethnicity | Age at Disease Onset | Age at ESKD | Gene Symbol | Inheritance | Exon Number | Nucleotide Change | Protein Effect | Allele Frequency | Zygosity | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pathogenic podocyte gene variants | ||||||||||||
| 2517 (F4) | M | Admixed | unk | 14 | LMX1B | AD | 4 | c.668G>A | Arg223Gln | 0 | Het | S40–S44 |
| 2518 (F4) | M | Admixed | unk | 18 | LMX1B | AD | 4 | c.668G>A | Arg223Gln | 0 | Het | S40–S44 |
| 5496 (F7) | M | EAS | 16 | 22 | COQ8B | AR | 15 | c.1356_1362del | Gln452Hisfs | 0 | Homo | S45 |
| 5497 (F7) | F | EAS | 21 | n/a (30) | COQ8B | AR | 15 | c.1356_1362del | Gln452Hisfs | 0 | Homo | S45 |
| 5935 (F9) | F | EUR | unk | unk | INF2 | AD | 2 | c.312C>G | Cys104Trp | 0 | Het | S46 |
| 5936 (F9) | F | EUR | unk | unk | INF2 | AD | 2 | c.312C>G | Cys104Trp | 0 | Het | S46 |
| 6996 (F21) | M | Admixed | 25 | n/a (51) | NPHS1 | AR | 22 | c.2928G>T | Arg976Ser | 4.87E-05 | Homo | S47–S51 |
| 2378 (s) | M | EUR | 22 | 23 | INF2 | AD | 2 | c.317G>C | Arg106Pro | 0 | Het | S46 |
| 2745 (s) | F | EAS | 11 | n/a (20) | LMX1B | AD | 4 | c.737G>A | Arg246Gln | 0 | Het | S52–S54 |
| 5601 (s) | F | EUR | 24 | unk | LMX1B | AD | 4 | c.737G>A | Arg246Gln | 0 | Het | S52–S54 |
| 6251 (s) | F | EUR | 40 | n/a (49) | NPHS2 | AR | 7 | c.868G>A | Val290Met | 1.20E-04 | Homo | S55–S58 |
| Pathogenic CAKUT gene variants | ||||||||||||
| 7942 (s) | M | EUR | 55 | n/a (59) | BMP4 | AD | 2 | c.272C>G | Ser91Cys | 1.90E-04 | Het | S59, S60 |
The following minor allele frequency (MAF) cut-offs as determined in gnomAD (http://gnomad.broadinstitute.org/) were used for dominant and recessive disease genes respectively: 0.00005 and 0.005 (accessed February 22, 2018). The INF2 variant in 2378 was shown to be de novo by examining parental sequence data. The MAF of the BMP4 variant exceeds the cut-off, but it has been shown to be functionally hypomorphic. Patients 2517 and 2518 are son and father. Patients 5496 and 5497 are siblings. The relationship of patients 5935 and 5936 is unknown. (F) designates family pedigree number whereas (s) indicates a sporadic case. Het indicates heterozygous and homo indicates homozygous. All references refer to the supplemental reference list, which can be found in the Supplemental Material, and indicate previous reports of the variant and indicate previous reports of the variant. Age at kidney disease was indicated as n/a for patients without kidney disease, followed by their age at time of analysis in parentheses. Unk indicates that data were unavailable. M, male; EAS, East Asian; F, female; EUR, European.