Genotypes and phenotypes of 39 patients (34 families) with mutations in NPHP1, INVS, NPHP3, NPHP4, IQCB1, CEP290, RPGRIP1L and TMEM67
| Patient | Kidney ESRD (years) | Extrarenal manifestations | Origin | Gene | Nucleotide change* (zygosity) | Amino acid change (segregation) | Mutation count/coverage | Reference |
|---|---|---|---|---|---|---|---|---|
| A2548-21 | NPHP (6) | Turkey | NPHP1 | c.1884+1G>A (hom) | splice site | 717/728 (98.5%) | 35 | |
| A3336-21 | −21 infantile NPHP (2) | Egypt | INVS | c.2719C>T (hom) | p.R907* | 714/963 (74.1%) | 7 | |
| −22 infantile NPHP (3) | RD | NA | ||||||
| A3112-21 | infantile NPHP (1) | HM, DPM, sclerosing cholangiopathy | UK | NPHP3 | c.406delA (hom) | p.T136Rfs*13 | 25/55 (45.5%) | novel |
| A2240 | −21 infantile NPHP (at birth) | liver cysts, pancreas cysts, died at 6 months | The Netherlands | NPHP3† | c.434_437delAAAG (het) | p.E145Vfs*3 (m) | 74/163 (45.4%) | novel |
| –22 infantile NPHP (at birth) | liver cysts, pancreas cysts, SI, died at 6 months | NA | ||||||
| A173-21 | infantile NPHP (1) | HF, BDP | USA | NPHP3 | c.537_542delAGAAAA (het) | p.K179_E180del (de novo) | 151/279 (54.1%) | novel |
| c.2570+1G>T (het) | splice site (m) | 368/672 (54.8%) | novel | |||||
| A2184-21 | Infantile NPHP (at birth) | SI, died at 6 months | Brazil | NPHP3† | c.3373C>T (het) | p.R1125* | 487/1138 (42.8%) | novel |
| A2225-21 | Infantile NPHP (0.5) | MR, HF | Turkey | NPHP3 | c.3567_3568delAA (hom) | p.K1189Nfs*5 | 333/342 (97.4%) | novel |
| A1451-24 | Infantile NPHP (2) | sib died age 6 years | Egypt | NPHP3 | c.3812+1G>C (hom) | splice site (m, p) | 393/405 (97%) | novel |
| A2393-21 | SLS (25) | RD | Italy | NPHP4 | c.175C>T (hom) | p.R59* | 311/314 (99%) | 35 |
| A1052-21 | SLS (40) | RD | The Netherlands | NPHP4† | c.1763+1G>A (het) | splice site | 303/605(50%) | novel |
| F116-21 | NPHP (9) | Greece | NPHP4† | c.1839delTinsGA (het) | p.N613Kfs*5 (m) | 167/376 (44.4%) | novel | |
| F1348-21 | SLS (12) | RD | Germany | NPHP4† | c.1956−2A>G (het) | splice site | 40/125 (32%) | novel |
| F62 | −21 (no NPHP at age 11) | LCA, MR, ichthyosis, spastic dysplegia, Sjogren's syndrome | Germany | IQCB1 | c.224_225delTT (het) | p.F142Pfs*5 (m) | 344/770 (44.7%) | 11 |
| −22 SLS (7) | LCA | c.1518_1519delCA (het) | p.H506Qfs*13 (p) | 133/291 (45.7%) | 11 | |||
| A3618-21 | SLS (19) | RD | UK | IQCB1 | c.224_225delTT (hom) | p.F142Pfs*5 | 904/929 (97.37%) | 11 |
| A1973-22 | SLS (13) | RD | USA | IQCB1 | c.897-900dupCTTG (het) | p.I301Lfs*42 (m) | 172/227 (75.8%) | novel |
| c.224_225delTT (het) | p.F142Pfs*5 (p) | 437/885 (49.4%) | 11 | |||||
| F849-21 | SLS (51) | RD | France | IQCB1 | c.758delG (het) | p.C253Sfs*9 | 462/1376 (33.6%) | novel |
| c.1381C>T (het) | p.R461* | 39/172 (22.7%) | 11 | |||||
| A1902 | −21 SLS (43) | RD | Austria | IQCB1 | c.1518_1519delCA (het) | p.H506Qfs*13 | 132/303 (43.6%) | 11 |
| −22 LCA, (no NPHP at age 46) | LCA, central hypertonia | c.825_828delACAG (het) | p.R275Sfs*6 | 142/323 (44%) | 11 | |||
| F58 | −21 SLS (33) | LCA | The Netherlands | IQCB1 | c.897_900dupCTTG (het) | p.I301Lfs*42 | 230/277 (83%) | novel |
| −24 SLS (30) | LCA | c.1333C>T (het) | p.R445* | 443/897 (49.4%) | novel | |||
| A3084-21 | SLS(13) | LCA | Germany | IQCB1 | c.994C>T (het) | p.R332* | 14/28 (50%) | 11 |
| c.1518_1519delCA (het) | p.H506Qfs*13 | 4/9 (44.4%) | 11 | |||||
| A2378-21 | SLS (11) | LCA, ASD | Saudi Arabia | IQCB1 | c.1130−1G>C (hom) | splice site | 1732/1745 (99.3%) | novel |
| A2227-21 | SLS (15) | LCA, ASD | USA | IQCB1 | c.1518_1519delCA (hom) | p.H506Qfs*13 | 371/387 (95.9%) | 11 |
| F1150-21 | SLS (7) | LCA | USA | IQCB1 | c.1518_1519delCA (hom) | p.H506Qfs*13 | 288/300 (96%) | 11 |
| F263-22 | SLS (17) | RD | Germany | IQCB1† | c.1518_1519delCA (het) | p.H506Qfs*13 | 145/369 (39.3%) | 11 |
| A1664-21 | SLS (13) | RD | Canada | CEP290 | c.95T>C (het) | p.L32S | 292/1186 (24.6%) | novel |
| c.5226+5_8delGTAA (het) | splice site | 115/570 (20.2%) | novel | |||||
| F283-21 | SLS (18) | RD | Germany | CEP290‡ | c.1984C>T (het) | p.Q662* | 366/805 (45.5%) | 37 |
| c.4723A>T (het) | p.K1575* | Sanger | 38 | |||||
| A3100-21 | SLS (16) | RD, MR | Slovenia | CEP290‡ | c.1987A>T (het) | p.K663* | 389/966 (40.3%) | novel |
| c.4723A>T (het) | p.K1575* | Sanger | 38 | |||||
| A1210-21 | SLS (22) | LCA | Germany | CEP290‡ | c.3802C>T (het) | p.Q1268* (m) | 33/55 (60%) | novel |
| c.4723A>T (het) | p.K1575* | Sanger | 38 | |||||
| F118-21 | SLS (11) | RD | Germany | CEP290‡ | c.4452_4455delAGAA (het) | p.K1484Nfs*4 | 33/63 (52.4%) | novel |
| c.4723A>T (het) | p.K1575* | Sanger | 38 | |||||
| A1712-21 | SLS (NA) | RD | Germany | CEP290‡ | c.1189+1G>A | splice site | Sanger | novel |
| c.4723A>T (het) | p.K1575* | 6/13 (46.2%) | 38 | |||||
| A711-21 | SLS(NA) | LCA | Canada | CEP290† | c.4966G>T (het) | p.E1656* | 95/355 (26.8%) | 39 |
| A2-21 | SLS (6) | LCA | Australia | CEP290‡ | c.270_274delAGTAA (het) | p.K90Nfs*6 | Sanger | novel |
| c.6277delG (het) | p.V2093Sfs*4 | 49/88 (56%) | 40 | |||||
| A2156-21 | JBTS (no NPHP at age 1 year) | central hypotonia, PD, VUR, microcephaly | USA | RPGRIP1L† | c.1700−1G>A (het) | splice site | 208/407 (51.1%) | novel |
| A382-21 | SLS (NA) | RD | Italy | TMEM67 | c.622A>T (het) | p.R208* | 103/163 (63.2%) | 41 |
| c.1289A>G (het) | p.D430G | 69/159 (43.4%) | novel | |||||
| F912-21 | NPHP (23) | iris coloboma, optic nerve coloboma, SMR, autism | Germany | TMEM67 | c.622A>T (het) | p.R208* (p) | 66/110 (60%) | 41 |
| c.2498T>C (het) | p.I833T (m) | 295/675(43.7%) | 42 |
*All mutations were absent from at least 96 healthy control subjects. Mutation numbering is based on cDNA position according to table 1 with +1 corresponding to the A of the ATG translation initiation codon.
†Only one mutated allele has been identified despite Sanger sequencing of all exons of the respective gene.
‡Second mutated allele has been identified by Sanger sequencing.
ASD, atrial septal defect; BDP, bilary ductal proliferation; DPM, ductal plate malformation; ESRD, end-stage renal disease; (het), heterozygous mutation; (hom), homozygous mutation; HF, hepatic fibrosis; HM, hepatomegaly; HT, muscle hypotonia; LCA, Leber congenital amaurosis; (m), maternal heterozygous mutation; MR, mental retardation; NA, no data available; (p), paternal heterozygous mutation; PD, polydactyly; RD, retinal dystrophy; SI, situs inversus; SMR, statomotor retardation; VUR, vesicoureteral reflux.