Table 3

Genotypes and phenotypes of 38 patients (30 families) with mutations in NPHP4, IQCB1, CEP290, RPGRIP1L, TMEM67, AHI1, CC2D2A, and TTC21B and respective MPR statistics

PatientDiagnosisKidney ESRD (yrs)EyeBrainLiverOtherOriginGeneNucleotide change* (zygosity state)Amino acid change (segregation)Mutant allele frequencyMutation assignmentReference
F962-23NPHPNPHP (12)GermanyNPHP4c.3364A→C (h)p.T1122P (p)90/6163 (1.5%)CEL INovel
c.305delA (h)p.N102fsX76 (m)14/684 (2.0%)CEL INovel
F698−21: NPHPNPHP (21)BelgiumNPHP4c.3068G→A (h)p.W1023X (m)43/1694 (2.5%)CEL INovel
−22: NPHPNPHP (11)c.3403delC (h)p.R1135fsX1056/7148 (0.8%)CEL INovel
A394−21: SLSRD, NysGermanyIQCB1c.1090C→T (h)p.R364X77/3945 (2.0%)CEL I neg.Novel
−22: SLSNPHP (10)LCA, NysSeq 15 exons
F15−21: SLSNPHP (11)LCA, NysAtx, MRFranceCEP290c.5649–50insA (h)p.L1884fsX23 (p)NASeq 53 exons32
−24: SLSNPHP (15)LCAAtx, MRc.5850delT (h)p.F1950fsX15 (m)34/4784 (0.7%)CEL I33
F335−22: SLSNPHP (13)LCAFranceCEP290c.2915T→C (H)p.L972P (p, m)63/2404 (2.6%)CEL I neg.Novel
−25: SLSNPHP (>3)LCA
F394-27JBTSNPHP (4)RD, Nys, ColCVA, Atx, MRMicCepTurkeyCEP290c.5668G→T (H)p.G1890X (§, m)67/3316 (2.0%)CEL I10
A1188-21JBTSNPHP (12)CVA, MRPakistaniCEP290c.5668G→T (H)p.G1890X36/1028 (3.5%)CEL I10
A2029-21JBTSNPHP (2)LCAMTS, MRHFUSACEP290c.5668G→T (h)p.G1890X92/5460 (1.7%)Dir. seq.10
c.1189G→A (h)p.G397S33/3408 (1.0%)CEL INovel
A1388-21JBTSNPHP (8)NysCVA, MRdeafnessGermanyCEP290c.5649–50insA (h)p.L1884fsX23NASeq 53 exons32
c.136G→T (h)p.E46X99/3565 (2.8%)Dir. SeqNovel
A1713-21−21: JBTSNPHPLCACVHdied 3 yrsGermanyCEP290c.6277delG (h)p.V2093fsX49/373 (2.4%)CEL I neg.34
−22: JBTSNPHPLCACVHc.5182G→T (h)p.E1728X5/229 (2.2%)Dir. SeqNovel
A1715-21JBTSNPHP (10)RDMR, OphCFAIndiaCEP290c.5445–8delAACT (h)p.L1815fsX4 (p)NASeq 53 exonsNovel
c.5311G→T (h)p.E1771X (m)9/370 (2.4%)CEL I neg.Novel
A2420−21: MKSMDKOECHDDUKCEP290c.1451delA (h)p.K484fsX833/4111 (0.8%)CEL INovel
−22: MKSMDKOECHDDSeq 18 exons
A2424−21: MKSMDKOEC, DWMPDUKRPGRIP1Lc.1829A→C (h)p.H610P83/4463 (1.9%)CEL INovel
−22: MKSMDKOEC, DWMPDc.721–4delAATG (h)p.N241fsX25NASeq 26 exonsNovel
F90-21JBTSNPHP (4)Nys, RDCVA, MR, Atx,HFPD, MicCepGermanyTMEM67c.1843T→C (h)p.C615R39/843 (4.6%)CEL I neg.35
c.755T→C (h)p.M252T (p)36/1243 (2.9%)CEL I36
F96-22JBTSNPHP (22)Col, RDCVA, MR, AtxGermanyTMEM67c.755T→C (h)p.M252T (m)42/1538 (2.7%)CEL I36
c.2498T→C (h)p.I833T (p)165/13292 (1.2%)CEL I37
F278-21JBTSNPHP (14)Atx, MRHF, CPGermanyTMEM67c.1843T→C (h)p.C615R234/6373 (3.7%)CEL I neg.35
c.755T→C (h)p.M252T13/1409 (0.9%)CEL I36
F315-21JBTSNPHP (9)NysCVH, MRHFGermanyTMEM67c.1843T→C (h)p.C615R234/6373 (3.7%)CEL I neg.35
c.1911C→A (h)p.F637L17/1115 (1.5%)CEL INovel
F480-22JBTSNPHP (0.2)CVHGermanyTMEM67c.1387C→T (h)p.R463X (m)7/320 (2.2%)Dir. SeqNovel
c.2891C→T (h)p.T964I (p)10/528 (1.9%)CEL INovel
F459-22JBTSNPHP (30)ColCVH, ATX, MRHF, BDPhearing lossUSATMEM67c.986A→C (h)p.K329T (p)95/3313 (2.9%)CEL INovel
c.2556+1G→A (h)splice172/10393 (1.7%)CEL INovel
F631-21JBTSNPHP (21)ColMR,HFGermanyTMEM67c.1045T→C (h)p.L349SNASeq 28 exons36
c.1843T→C (h)p.C615R (p)39/843 (4.6%)CEL I neg.35
A77-21JBTSNPHP (7)OACVH, MRHFaortic stenosisGermanyTMEM67c.622A→T (h)p.R208X123/6069 (2.0%)CEL I36
c.2168A→G (h)p.Y723C (m)13/905 (1.4%)CEL INovel
A971-21JBTSNPHP (7)NysCVH, MR, AtxHF, CPGermanyTMEM67c.622A→T (h)p.R208XNASeq 28 exons36
c.1843T→C (h)p.C615R234/6373 (3.7%)CEL I neg.35
A3208-21JBTSNPHP (28)ColMTS, MRepilepsyUKTMEM67c.1351C→T (h)p.R451X75/5041 (1.5%)CEL I38
c.2018T→C (h)p.V673A270/13865 (1.9%)CEL INovel
F787-21JBTSCVHGermanyAHI1c.2671C→T (h)p.R891X112/4540 (2.5%)CEL INovel
Seq 28 exons
F434-21JBTSOMACCVH, HT, Atx, MRGermanyCC2D2Ac.517C→T (h)p.R173X (p)63/3771 (1.7%)Dir. Seq39
c.1676T→C (h)p.L559P (m)67/6139 (1.1%)CEL INovel
A2421-21MKSMDKOECHDDUKCC2D2Ac.3544T→C (h)p.W1182R5/500 (1.0%)CEL INovel
c.3774_5insT (h)p.E1259fsX1NASeq 35 exonsNovel
A2426-21MKSMDKOECCFA, OHyUKCC2D2Ac.685_7delGAA (h)p.E229delNASeq 35 exonsNovel
c.3893T→A (h)p.V1298D295/18699 (1.6%)CEL INovel
F244-25infantile NPHPNPHP (1.5)MR, OphHFSI, VC, BroTurkeyTTC21Bc.626C→T (h)p.P209L (m)334/11391 (2.9%)Dir. SeqDavis et al, submitted, 2010
c.1654–7delTGTC (h)p.C552fsX1 (p)NASeq 29 exonsDavis et al, submitted, 2010
F514-−21: NPHPNPHP (7)PSCSwissTTC21Bc.448T→C (h)p.W150R (m)53/5802 (0.9%)CEL IDavis et al, submitted, 2010
−22: NPHPNPHP(2)PSCSI, VURc.3264–3C→G (h)splice site (p)NASeq 29 exonsDavis et al, submitted, 2010
A34-21infantile NPHPNPHP (2)RDHFSI, short phalangesPortugueseTTC21Bc.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. SeqDavis 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.