Table 4.
Pathogenic variants detected in 362 families (371 patients) with proteinuria and hematuria with an age of onset <25 years in 23 genes that cause nephrotic syndrome if mutated
| Family | Exon (Zygo- sity) | Nucleotide change | Amino acid change | dbSNP (rs #) | Conserved to | Poly- phen 2 | SIFT | Muta- tion taster | Sex | Ethnicity (consan- guinity) | gnOMAD general population | gnO-MAD closest ethnicity | Bio- base | Method |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ACTN4 | ||||||||||||||
| A1055 | 14 (Het) | c. 1606C>A | P.Arg536Ser | − | Dr | 0.933 | Del | DC | M | Kurd (Y) | − | − | Novel | EXM |
| ARHGDIA | ||||||||||||||
| A1432 | 5 (Hom) | c.518G>T | p.Gly173Val | − | Sc | 1 | Del | DC | F | Jewish (Y) | 1/246016 (0 hom) | 1/9840 (0 hom) | [42] | PCR |
| 5 (Hom) | c.518G>T | p.Gly173Val | − | Sc | 1 | Del | DC | M | Jewish (Y) | 1/246016 (0 hom) | 1/9840 (0 hom) | [42] | PCR | |
| COQ2 | ||||||||||||||
| A103 | 3 (Het) | c.683A>G | p.Asn228Ser | 121918232 | Ce | 0.918 | Tol | DC | F | Euro (N) | 32/276228 (0 hom) | 0/111262 (0 hom) | [16, 43] | PCR |
| 5 (Het) | c.856C>T | p.Leu286Phe | 776124921 | Dm | 0.997 | Del | DC | 2/245656 (0 hom) | 2/111470 (0 hom) | [16] | PCR | |||
| CUBN | ||||||||||||||
| A1213 | 19 (Hom) | c. 2613_2614del | p.Asp872Leu*3 | 386833777 | NA | NA | NA | NA | M | Balkan (N) | 6/276980 (0 hom) | 0/126554 (0 hom) | [44] | EXM |
| 19 (Hom) | c. 2613_2614del | p.Asp872Leu*3 | 386833777 | NA | NA | NA | NA | M | Balkan (N) | 6/276980 (0 hom) | 0/126554 (0 hom) | [44] | EXM | |
| 19 (Hom) | c. 2613_2614del | p.Asp872Leu*3 | 386833777 | NA | NA | NA | NA | M | Balkan (N) | 6/276980 (0 hom) | 0/126554 (0 hom) | [44] | EXM | |
| INF2 | ||||||||||||||
| A675 | 2 (Het) | c.37G>A | p.Ala13Thr | 201383094 | Dr | 0.982 | Tol | DC | F | Euro (N) | 85/240928 (1 hom) | 40/106632 (0 hom) | [45]a | PCR |
| LAMB2 | ||||||||||||||
| A1757 | 2 (Hom) | c.143A>C | p.Tyr48Ser | 776905329 | Dr | 1 | Del | DC | M | Hisp (N) | 9/239510 (0 hom) | 0/33384 (0 hom) | Novel | EXM |
| 2 (Hom) | c.143A>C | p.Tyr48Ser | 776905329 | Dr | 1 | Del | DC | F | Hisp (N) | 9/239510 (0 hom) | 0/33384 (0 hom) | Novel | EXM | |
| A2356 | 7 (Hom) | c.736C>T | p.Arg246Trp | 121912488 | Ce | 1 | Del | DC | M | Asian (Y) | 3/240414 (0 hom) | 0/17184 (0 hom) | [16, 46] | PCR |
| A1613 | 10 (Hom) | c.1405 + 1G>A | Splice | 780041521 | NA | −100% | 0% | −100% | M | Euro (N) | 4/244056 (0 hom) | 1/109858 (0 hom) | [16, 47] | PCR |
| LMX1B | ||||||||||||||
| A200 | 4 (Het) | c.737G>A | p.Arg246Gln | − | Ce | 1 | Del | DC | F | Turk (Y) | − | − | [16, 48] | PCR |
| A2175 | 4 (Het) | c.737G>A | p.Arg246Gln | − | – | 1 | Del | DC | M | Euro (N) | − | − | [16, 48] | PCR |
| A3180 | 4 (Het) | c.737G>A | p.Arg246Gln | − | Ce | 1 | Del | DC | F | Euro (N) | − | − | [16, 48] | PCR |
| A4009 | 7 (Het) | c.929C>G | p.Thr310Arg | − | Gg | 0.701 | Del | DC | F | Arabic (Y) | − | − | Novela | PCR |
| NPHS1 | ||||||||||||||
| A1803 | 2 (Hom) | c.139delG | p.Ala47Pro*81 | 386833882 | NA | NA | NA | NA | M | Cauc (N) | 2/241678 (0 hom) | 1/107982 (0 hom) | Novela | PCR |
| A3775 | 7 (Het) | c.840 + 1G>T | Splice | − | NA | −100% | −100% | −100% | F | Indian (N) | 1/245036 (0 hom) | 1/30778 (0 hom) | [49]a | PCR |
| 21 (Het) | c.2903G>T | p.Gly968Val | 771798618 | Ce | 1 | Del | DC | 1/236378 (0 hom) | 0/30014 (0 hom) | Novela | PCR | |||
| A3380 | 8 (Het) | c.928G>A | p.Asp310Asn | 763972372 | Dm | 0.99 | Del | DC | M | Asian (N) | 3/241700 (0 hom) | 3/17218 (0 hom) | [50, 51] | PCR |
| 21 (Het) | c.2816-3T>G | Splice | − | NA | −91.9% | −77.2% | −2.9% | − | − | [16, 51] | PCR | |||
| B115 | 12 (Hom) | c.1555C>T | p.Pro519Ser | − | Dr | 0.984 | Tol | PMP | F | Cauc (N) | − | − | [52] | EXM |
| A1500 | 20 (Hom) | c.2728T>C | p.Ser910Pro | − | Dr | 0.959 | Del | DC | F | Afr-Am (N) | − | − | [53, 54] | PCR |
| NPHS2 | ||||||||||||||
| A4681 | 1 (Hom) | c.1A>T | p.Met1* | − | NA | NA | NA | NA | F | Arabic (Y) | − | − | [16] | EXM |
| A4624 | 4 (Hom) | c.467dup | p.Leu156Phe*11 | − | NA | NA | NA | NA | F | Arabic (Y) | − | − | [17, 51, 55, 56] | PCR |
| B188 | 7 (Hom) | c.855-856del | p.Arg286Thr*17 | 749740335 | NA | NA | NA | NA | F | Hisp (Y) | 18/275798 (0 hom) | 0/34342 (0 hom) | [57, 58]a | PCR |
| A1616 | 7 (Hom) | c.868G>A | p.Val290Met | 200482683 | Dr | 0.998 | Del | DC | F | Cauc (N) | 33/276038 (0 hom) | 32/126036 (0 hom) | [59–61] | PCR |
| A2239 | 8 (Hom) | c.926C>T | p.Ala309Val | − | Ce | 0.742 | Del | DC | M | Turk (N) | − | − | [62]a | PCR |
| PLCE1 | ||||||||||||||
| A3233 | 10 (Hom) | c.3169C>T | p.Arg1057* | − | NA | NA | NA | NA | F | Arabic (Y) | 1/245964 (0 hom) | 0/111494 (0 hom) | [16] | PCR |
| A3617 | 11 (Hom) | c.3379_3380del | p.Asn1127* | − | NA | NA | NA | NA | F | Arabic (Y) | − | − | [16] | PCR |
| A3510 | 20 (Hom) | c.4600A>G | p.Lys1534Glu | − | Sc | 0.998 | Del | DC | F | Turk (Y) | − | − | [16] | PCR |
| A3869 | 26 (Hom) | c.5521A>G | p.Lys1841Glu | − | Sc | 1 | Del | DC | M | Arabic (Y) | − | − | [16] | PCR |
| SMARCAL1 | ||||||||||||||
| A3146 | 4 (Het) | c.49C>T | p.Arg17* | 119473034 | NA | NA | NA | NA | F | Euro (N) | 2/246210 (0 hom) | 1/111680 (0 hom) | [63]a | PCR |
| 5 (Het) | c.836T>C | p.Phe279Ser | 775057827 | Ci | 0.985 | Tol | DC | 28/277230 (0 hom) | 23/126712 (0 hom) | [64]a | PCR | |||
| A4162 | 12 (Hom) | c.1736C>A | p.Ser579* | − | NA | NA | NA | NA | F | Euro (N) | − | − | [16] | PCR |
| TRPC6 | ||||||||||||||
| A4685 | 2 (Het) | c.523C>T | p.Arg175Trp | − | Dr | 1 | Del | DC | F | Arabic (N) | − | − | [17] | EXM |
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. The splice site prediction scores were derived left to right from the MaxEnt, NNSPLICE and HSF prediction programs, respectively.
Afr-Am, African American; Cauc, Caucasian; Ce, Caenorhabditis elegans; Ci, Ciona intestinalis; DC, disease causing; Dr, Danio rerio; Del, deleterious; Dm, Drosophila melanogaster; dup, duplication; Euro, European; F, female; EXM, homozygosity mapping and whole exome sequencing; Gg, Gallus gallus; Het, heterozygous; Hisp, hispanic; Hom, Homozygous; M, male; N, no; NA, not applicable; PCR, Fluidigm multiplex PCR + NGS; PMP, polymorphism; Sc, Saccharomyces cerevisiae; Tol, tolerated; Turk, Turkish; Y, yes.