Table 2.
Genotype and phenotype of mutations in recessive steroid-resistant nephrotic syndrome -causing genes detected in Chinese children with steroid-resistant nephrotic syndrome#
| patient | Nucleotide alteration | Deduced protein change | Location (Zygosity, segregation) | Gender | Age at onset | kidney disease | Biopsy (at age) | Extrarenal presentations | Follow up (at age) | Ref |
|---|---|---|---|---|---|---|---|---|---|---|
| NPHS1 (accession no: NM_004646.3) | ||||||||||
| 22 | c.313G>A | p.Asp105Asn | EX3 (het) | F | 5 mo | NS | MCD(6 mo) | No | Normal renal function (10 mo) | 20 |
| c.385C>T | p.Leu129Phe | EX3 (het) | 21 | |||||||
| 1 | c.802C>T | p.R268* | EX7 (het) | F | 1d | NS | ND | Atrial septal defect | Died | 22 |
| c.3325C>T | p.Arg1109* | EX26 (het) | 23 | |||||||
| 6 | c.928G>A | p.Asp310Asn | EX8 (het, m) | M | 13d | SRNS | ND | Umbilical hernia | ND | 24 |
| c.1931-1_1931insT | p.Tyr644Leufs*30 | EX15 (het, f) | Novel | |||||||
| 10 | c.967G>T | p.Val323Leu | EX8 (het, m) | F | 34d | SRNS | FSGS(8 yrs, 15 yrs) | No | Normal renal function (17 yrs) | Novel |
| c.1570G>A | p.Ala524Thr | EX12 (het, f) | Novel | |||||||
| 2 | c.2663G>A | p.Arg888Lys | EX19 (het, m) | M | 2d | NS | ND | Small for gestational age | ND | Novel |
| c.3286+5G>A | Splice | IVS24 (het, f) | Novel | |||||||
| 8 | c.3027C>G | p.Tyr1009* | EX22 (het) | M | 19d | NS | ND | Premature infant, enlarged placenta | ND | Novel |
| c.3478C>T | p.Arg1160* | EX27 (het) | 25 | |||||||
| 9 | c.3118C>T | p.Gln1040* | EX23 (het, m) | M | 24d | NS | ND | Bilateral inguinal hernia, enlarged placenta | Died (1 yr) | Novel |
| c.3325C>T | p.Arg1109* | EX26 (het, f) | 23 | |||||||
| NPHS2 (accession no: NM_014625.2) | ||||||||||
| 34 | c.211C>T | p.Arg71* | EX1 (hom) | M | 3 yrs 5 mo | SRNS | FSGS(3 yrs 9 mo) | Right inguinal hernia | ESRD (10 yrs 4 mo) | 26 |
| 29 | c.211C>T | p.Arg71* | EX1 (het, f) | F | 2 yrs 5 mo | SRNS | ND | ND | ESRD (7 yrs 8 mo) | 26 |
| c.467_468insT | p.Leu156Phefs*11 | EX4 (het, m) | 27 | |||||||
| 32 | c.412C>T | p.Arg138* | EX3 (het) | F | 2 yrs 10 mo | SRNS | ND | ND | ND | 28 |
| c.535-1G>A | splice | IVS4 (het) | Novel | |||||||
| 41 | c.467_468insT | p.Leu156Phefs*11 | EX4 (het, f) | M | 2 yrs | SRNS | ND | Left testiculus dysplasia | ESRD (6 yrs 1 mo) | 27 |
| c.738+2T>C | splice | IVS5 (het, m) | Novel | |||||||
| ADCK4 (accession no: NM_024876.3) | ||||||||||
| 119 | c.241G>T | p.Glu81* | EX4 (het, m) | M | 11 yrs | nephrotic-level proteinuria, steroid resistant | FSGS (11 yrs) | Low level of of serum C3 concentration | Normal renal function (12 yrs) | Novel |
| c.1468C>T | p.Arg490Cys | EX15 (het, f) | Novel | |||||||
| 83 | c.448C>T | p.Arg150* | EX6 (het, m) | F | 8 yrs | SRNS | FSGS(10 yrs 9 mo) | ND | ESRD (11 yrs 8 mo) | Novel |
| c.748G>C | p.Asp250His | EX9 (het, f) | 29 | |||||||
| 117 | c.532C>T | p.Arg178Trp | EX7 (het, m) | F | 9 yrs 2 mo | SRNS | Sclerosing glomerulonephritis (9 yrs 2 mo) | ND | ESRD (11 yrs) | 30 |
| c.748G>C | p.Asp250His | EX9 (het, f) | 29 | |||||||
| 82 | c.737G>A | p.Ser246Asn | EX9 (hom, f, m) | F | 8 yrs 2 mo | SRNS | FSGS(8 yrs 10 mo) | ND | Normal renal function (9 yrs 2 mo) | Novel |
| 120 | c.737G>A | p.Ser246Asn | EX9 (hom, f, b) | F | 17 yrs 4 mo | proteinuria | MsPGN (18 yrs 10mo) | ND | Normal renal function (18 yrs 10 mo) | Novel |
| 4 | c.748G>C | p.Asp250His | EX9 (hom, f, m) | F | 10d | NS | ND | ND | ND | 29 |
| 30 | c.748G>C | p.Asp250His | EX9 (hom, f, m) | F | 1 yr 7 mo | SRNS | FSGS(1 yr 7 mo) | ND | ESRD (6 yrs) | 29 |
| 16 | c.748G>C | p.Asp250His | EX9 (het, m) | F | 6 yrs | proteinuria | FSGS(10 yrs) | ND | Normal renal function (12 yrs) | 29 |
| c.1093C>G | p.Gln365Glu | EX12 (het, f) | Novel | |||||||
| CUBN (accession no: NM_001081.3) | ||||||||||
| 53 | c.4837C>T | p.Arg1613* | EX32 (het, m) | F | 1 yr 6 mo | SRNS | MsPGN(1 yr 6 mo) | ND | Normal renal function (11 yrs 6 mo) | Novel |
| c.8938G>A | p.Asp2980Asn | EX57 (het, f) | Novel | |||||||
| 36 | c.7561C>G | p.Pro2521Ala | EX49 (het, m) | F | 2 yrs 8 mo | SRNS | ND | ND | ESRD (2 yrs 10 mo) | Novel |
| c.9335T>C | p.Phe3112Ser | EX59 (het, f) | Novel | |||||||
| LAMB2 (accession no: NM_002292.3) | ||||||||||
| 7 | c.2044_2045insTT | p.Cys682Phefs*13 | EX16 (hom, m, f) | F | 19d | NS | ND | Premature infant, bilateral myosis | ND | Novel |
| PLCE1 (accession no: NM_016341.3) | ||||||||||
| 13 | c.4301G>A | p.Arg1434Gln | EX17 (het, m) | M | 7 mo | SRNS | FSGS(1 yr 3 mo) | Movement development retardation | ESRD (11 mo) | Novel |
| c.4852G>T | p.Glu1618* | EX21 (het, f) | Novel | |||||||
| SMARCAL1 (accession no: NM_014140.3) | ||||||||||
| 66 | c.2443G>A | p.Glu815Lys | EX16 (het, not located in the same allele with p.Arg817His) | F | 5 yrs 11 mo | SRNS | FSGS(6 yrs) | Scattered cafe-au-lait-spots in right armpit and abdomen, growth retardation | Normal renal function (6 yrs 2 mo) | Novel |
| c.2450G>A | p.Arg817His | EX16 (het, not located in the same allele with p.Glu815Lys ) | Novel | |||||||
1. Patient 7 was Uighur, and the remainders were Han Chinese ethnicity.
2. Patients 6, 29, 32. 83, 117, 82, 120, 4, 30 and 16 had a positive family history with proteinuria and/or renal failure, and the remainders had a negative family history with proteinuria and/or renal failure.
3. Except that disease did not reoccur after patient 117 underwent renal transplantation, no data of disease recurrence if transplanted in other patients were available.
Ref, Reference; EX, Exon; IVS, Intron; het, heterozygous; hom, homozygous; F, female; M, male; f: father; m: mother; b: brother; d, day; mo, month; yrs, years; NS, nephrotic syndrome; SRNS, steroid nephrotic syndrome; MCD, minimal change disease; FSGS, focal segmental glomerulosclerosis; MsPGN, mesangial proliferative glomerulonephritis; ND, no data or not done; ESRD, end-stage renal disease.