Genotypes and phenotypes of 38 patients (30 families) with mutations in NPHP4, IQCB1, CEP290, RPGRIP1L, TMEM67, AHI1, CC2D2A, and TTC21B and respective MPR statistics
| Patient | Diagnosis | Kidney ESRD (yrs) | Eye | Brain | Liver | Other | Origin | Gene | Nucleotide change* (zygosity state) | Amino acid change (segregation) | Mutant allele frequency | Mutation assignment† | Reference |
| F962-23 | NPHP | NPHP (12) | – | – | – | – | Germany | NPHP4 | c.3364A→C (h) | p.T1122P (p) | 90/6163 (1.5%) | CEL I | Novel |
| c.305delA (h) | p.N102fsX76 (m) | 14/684 (2.0%) | CEL I | Novel | |||||||||
| F698 | −21: NPHP | NPHP (21) | – | – | – | – | Belgium | NPHP4 | c.3068G→A (h) | p.W1023X (m) | 43/1694 (2.5%) | CEL I | Novel |
| −22: NPHP | NPHP (11) | – | – | – | – | c.3403delC (h) | p.R1135fsX10 | 56/7148 (0.8%) | CEL I | Novel | |||
| A394 | −21: SLS | – | RD, Nys | – | – | – | Germany | IQCB1 | c.1090C→T (h) | p.R364X | 77/3945 (2.0%) | CEL I neg. | Novel |
| −22: SLS | NPHP (10) | LCA, Nys | – | ‡ | ‡ | ‡ | Seq 15 exons | ‡ | |||||
| F15 | −21: SLS | NPHP (11) | LCA, Nys | Atx, MR | – | – | France | CEP290 | c.5649–50insA (h) | p.L1884fsX23 (p) | NA | Seq 53 exons | 32 |
| −24: SLS | NPHP (15) | LCA | Atx, MR | – | – | c.5850delT (h) | p.F1950fsX15 (m) | 34/4784 (0.7%) | CEL I | 33 | |||
| F335 | −22: SLS | NPHP (13) | LCA | – | – | – | France | CEP290 | c.2915T→C (H) | p.L972P (p, m) | 63/2404 (2.6%) | CEL I neg. | Novel |
| −25: SLS | NPHP (>3) | LCA | – | – | – | ||||||||
| F394-27 | JBTS | NPHP (4) | RD, Nys, Col | CVA, Atx, MR | – | MicCep | Turkey | CEP290 | c.5668G→T (H) | p.G1890X (§, m) | 67/3316 (2.0%) | CEL I | 10 |
| A1188-21 | JBTS | NPHP (12) | – | CVA, MR | – | – | Pakistani | CEP290 | c.5668G→T (H) | p.G1890X | 36/1028 (3.5%) | CEL I | 10 |
| A2029-21 | JBTS | NPHP (2) | LCA | MTS, MR | HF | – | USA | CEP290 | c.5668G→T (h) | p.G1890X | 92/5460 (1.7%) | Dir. seq. | 10 |
| c.1189G→A (h) | p.G397S | 33/3408 (1.0%) | CEL I | Novel | |||||||||
| A1388-21 | JBTS | NPHP (8) | Nys | CVA, MR | – | deafness | Germany | CEP290 | c.5649–50insA (h) | p.L1884fsX23 | NA | Seq 53 exons | 32 |
| c.136G→T (h) | p.E46X | 99/3565 (2.8%) | Dir. Seq | Novel | |||||||||
| A1713-21 | −21: JBTS | NPHP | LCA | CVH | – | died 3 yrs | Germany | CEP290 | c.6277delG (h) | p.V2093fsX4 | 9/373 (2.4%) | CEL I neg. | 34 |
| −22: JBTS | NPHP | LCA | CVH | – | – | c.5182G→T (h) | p.E1728X | 5/229 (2.2%) | Dir. Seq | Novel | |||
| A1715-21 | JBTS | NPHP (10) | RD | MR, Oph | – | CFA | India | CEP290 | c.5445–8delAACT (h) | p.L1815fsX4 (p) | NA | Seq 53 exons | Novel |
| c.5311G→T (h) | p.E1771X (m) | 9/370 (2.4%) | CEL I neg. | Novel | |||||||||
| A2420 | −21: MKS | MDK | – | OEC | HDD | – | UK | CEP290 | c.1451delA (h) | p.K484fsX8 | 33/4111 (0.8%) | CEL I | Novel |
| −22: MKS | MDK | – | OEC | HDD | – | ‡ | ‡ | ‡ | Seq 18 exons | ‡ | |||
| A2424 | −21: MKS | MDK | – | OEC, DWM | – | PD | UK | RPGRIP1L | c.1829A→C (h) | p.H610P | 83/4463 (1.9%) | CEL I | Novel |
| −22: MKS | MDK | – | OEC, DWM | – | PD | c.721–4delAATG (h) | p.N241fsX25 | NA | Seq 26 exons | Novel | |||
| F90-21 | JBTS | NPHP (4) | Nys, RD | CVA, MR, Atx, | HF | PD, MicCep | Germany | TMEM67 | c.1843T→C (h) | p.C615R | 39/843 (4.6%) | CEL I neg. | 35 |
| c.755T→C (h) | p.M252T (p) | 36/1243 (2.9%) | CEL I | 36 | |||||||||
| F96-22 | JBTS | NPHP (22) | Col, RD | CVA, MR, Atx | – | – | Germany | TMEM67 | c.755T→C (h) | p.M252T (m) | 42/1538 (2.7%) | CEL I | 36 |
| c.2498T→C (h) | p.I833T (p) | 165/13292 (1.2%) | CEL I | 37 | |||||||||
| F278-21 | JBTS | NPHP (14) | – | Atx, MR | HF, CP | – | Germany | TMEM67 | c.1843T→C (h) | p.C615R | 234/6373 (3.7%) | CEL I neg. | 35 |
| c.755T→C (h) | p.M252T | 13/1409 (0.9%) | CEL I | 36 | |||||||||
| F315-21 | JBTS | NPHP (9) | Nys | CVH, MR | HF | – | Germany | TMEM67 | c.1843T→C (h) | p.C615R | 234/6373 (3.7%) | CEL I neg. | 35 |
| c.1911C→A (h) | p.F637L | 17/1115 (1.5%) | CEL I | Novel | |||||||||
| F480-22 | JBTS | NPHP (0.2) | – | CVH | – | – | Germany | TMEM67 | c.1387C→T (h) | p.R463X (m) | 7/320 (2.2%) | Dir. Seq | Novel |
| c.2891C→T (h) | p.T964I (p) | 10/528 (1.9%) | CEL I | Novel | |||||||||
| F459-22 | JBTS | NPHP (30) | Col | CVH, ATX, MR | HF, BDP | hearing loss | USA | TMEM67 | c.986A→C (h) | p.K329T (p) | 95/3313 (2.9%) | CEL I | Novel |
| c.2556+1G→A (h) | splice | 172/10393 (1.7%) | CEL I | Novel | |||||||||
| F631-21 | JBTS | NPHP (21) | Col | MR, | HF | – | Germany | TMEM67 | c.1045T→C (h) | p.L349S | NA | Seq 28 exons | 36 |
| c.1843T→C (h) | p.C615R (p) | 39/843 (4.6%) | CEL I neg. | 35 | |||||||||
| A77-21 | JBTS | NPHP (7) | OA | CVH, MR | HF | aortic stenosis | Germany | TMEM67 | c.622A→T (h) | p.R208X | 123/6069 (2.0%) | CEL I | 36 |
| c.2168A→G (h) | p.Y723C (m) | 13/905 (1.4%) | CEL I | Novel | |||||||||
| A971-21 | JBTS | NPHP (7) | Nys | CVH, MR, Atx | HF, CP | – | Germany | TMEM67 | c.622A→T (h) | p.R208X | NA | Seq 28 exons | 36 |
| c.1843T→C (h) | p.C615R | 234/6373 (3.7%) | CEL I neg. | 35 | |||||||||
| A3208-21 | JBTS | NPHP (28) | Col | MTS, MR | – | epilepsy | UK | TMEM67 | c.1351C→T (h) | p.R451X | 75/5041 (1.5%) | CEL I | 38 |
| c.2018T→C (h) | p.V673A | 270/13865 (1.9%) | CEL I | Novel | |||||||||
| F787-21 | JBTS | – | – | CVH | – | – | Germany | AHI1 | c.2671C→T (h) | p.R891X | 112/4540 (2.5%) | CEL I | Novel |
| ‡ | ‡ | ‡ | Seq 28 exons | ‡ | |||||||||
| F434-21 | JBTS | – | OMAC | CVH, HT, Atx, MR | – | – | Germany | CC2D2A | c.517C→T (h) | p.R173X (p) | 63/3771 (1.7%) | Dir. Seq | 39 |
| c.1676T→C (h) | p.L559P (m) | 67/6139 (1.1%) | CEL I | Novel | |||||||||
| A2421-21 | MKS | MDK | – | OEC | HDD | – | UK | CC2D2A | c.3544T→C (h) | p.W1182R | 5/500 (1.0%) | CEL I | Novel |
| c.3774_5insT (h) | p.E1259fsX1 | NA | Seq 35 exons | Novel | |||||||||
| A2426-21 | MKS | MDK | – | OEC | – | CFA, OHy | UK | CC2D2A | c.685_7delGAA (h) | p.E229del | NA | Seq 35 exons | Novel |
| c.3893T→A (h) | p.V1298D | 295/18699 (1.6%) | CEL I | Novel | |||||||||
| F244-25 | infantile NPHP | NPHP (1.5) | – | MR, Oph | HF | SI, VC, Bro | Turkey | TTC21B | c.626C→T (h) | p.P209L (m) | 334/11391 (2.9%) | Dir. Seq | Davis et al, submitted, 2010 |
| c.1654–7delTGTC (h) | p.C552fsX1 (p) | NA | Seq 29 exons | Davis et al, submitted, 2010 | |||||||||
| F514- | −21: NPHP | NPHP (7) | – | – | PSC | – | Swiss | TTC21B | c.448T→C (h) | p.W150R (m) | 53/5802 (0.9%) | CEL I | Davis et al, submitted, 2010 |
| −22: NPHP | NPHP(2) | – | – | PSC | SI, VUR | c.3264–3C→G (h) | splice site (p) | NA | Seq 29 exons | Davis et al, submitted, 2010 | |||
| A34-21 | infantile NPHP | NPHP (2) | RD | – | HF | SI, short phalanges | Portuguese | TTC21B | c.2758–2A→G (h) | splice site (m) | 92/4905 (1.9%) | CEL I neg. | Davis et al, submitted, 2010 |
| c.626C→T (h) | p.P209L (p) | 334/11391 (2.9%) | Dir. Seq | Davis et al, submitted, 2010 |
↵* All mutations were absent from at least 96 healthy control subjects. Mutation numbering is based on cDNA position in reference sequences indicated in table 1 with +1 corresponding to the A of the ATG translation initiation codon.
↵† The mutation carrier assignment was performed by heteroduplex based CEL I endonuclease screening (CEL I) or by direct Sanger sequencing of the respective 24 DNA samples (Dir. Seq). In cases where CEL I analysis was inconclusive or negative (CEL I neg.) all 24 DNA samples from the respective pool were directly sequenced for one exon. In cases where only one mutated allele was found, all exons of the respective gene were sequenced and exon numbers are indicated (Seq # exons).
↵‡ Second mutation not detected.
↵§ No maternal or paternal DNA available.
Atx, ataxia; BDP, biliary ductal proliferation; Bro, bronchiectasis; CFA, craniofacial abnormalities; CP, cholangio-dysplasia; CVA, cerebellar vermis aplasia; CVH, cerebellar vermis hypoplasia; DWM, Dandy Walker malformation; ESRD, end stage renal disease; (h), heterozygous; (H), homozygous; HDD, hepatic developmental defects; HF, hepatic fibrosis; HT, muscle hypotonia; LCA, Leber congenital amaurosis; (m), heterozygous mutation identified in mother; MDK, multicystic dysplastic kidneys; MicCep, microcephaly; MR, mental retardation; MTS, molar tooth sign; NA, no data available; Nys, nystagmus; OA, opticus atrophy; OEC, occipital encephalocele; OHy, oligohydramnios; OMAC,oculomotor apraxia type Cogan; Oph, ophistotonus; (p), heterozygous mutation identified in father; PD, polydactyly; PSC, primary sclerosing cholangitis; RD, retinal dystrophy; SI, situs inversus; VC, vitium cordis; VUR, vesicoureteral reflux.