APPENDIX

Clinical Data and Spectrum of Detected Sequence Variants in 89 Patients With NSFL

VariableFamily No.Patient ReferenceGenderEthnicityConsanguinityAge of Onset, yFirst Clinical Presentation WithExtrarenal ManifestationsBiopsyTherapy and ResponseAge at Dialysis, yAge at KT, yESRD After AO, yNo ESRD After AO, yStatus Last SeenSequence VariantConsequence on ProteinMutation Reference
CNS
NPHS1
F2123MTurkishY0.0NSNNCNFNNDeceased[c.1135C>T] + [c.1135C>T][R379W] + [R379W]1
F2283MGermanN0.0DystrophyMental retardationDMSND3.44.23.4NAKT, functional[c.1738T>G] + [c.2479C>T][W580G] + [R827X]1
F2943MTurkishY0.0NS, EDNDND343NAKT, functional[IVS20 + 2T>A] + [IVS20 + 2T>A][Splice-site mutation] + [splice-site mutation]1
F4353MItalianNN0.0NSNNMCNSNNNNNNNNNNNN[c.2617delTCAinsCC] + [c.2617delTCAinsCC] + NPHS2: [c.686G>A][F873fsX904] + [F873fsX904] + NPHS2: [R229Q]2 + 3
F4393MGermanY0.0ED, prematureGrowth retardationNDND; NEC2.93.82.9NAKT, functional[c.1814delC] + [c.1814delC][A605fsX621] + [A605fsX621]1
F4513MGermanN0.0Elevated AFP, postnatal EDIntracerebral haemorrhageNNNNDeceased[c.468C>G] + [IVS27 + 1G>T] + NPHS2: [c.686G>A][Y156X] + [Splice-site mutation] + NPHS2: [R229Q]2 + 3
F475 II-13FGermanY0.0Acute ED at birthFailure to thriveMCNSSR1.84.81.8NAKT, relapse/ failure[c.2617delTCAinsCC] + [c.2617delTCAinsCC][F873fsX904] + [F873fsX904]2
F475 II-23FGermanY0.0Discrete ED at birthFailure to thriveNDSR; CSA: NR3.5NA3.5NAESRD, no KT[c.2617delTCAinsCC] + [c.2617delTCAinsCC][F873fsX904] + [F873fsX904]2
F571 II-13FTurkishN0.1Acute ED, HT, hypocalcemiaPyloric stenosis, bilateral hernia, connatal CMV infectionMCNSSR; CSA: NR<46<4NAKT, functional[c.1379G>A] + [c.1379G>A][R460Q] + [R460Q]2
F571 II-2MTurkishN0.0ED, HTNDNN5.5NA5.5NAESRD, no KT[c.1379G>A] + [c.1379G>A][R460Q] + [R460Q]2
F6263FTurkishY0.0Congenital SP, SGA, PU, HUSmall for gestational ageMPCGPSRDeceased[c.514 + 516delACC] + [c.514 + 516delACC][delT172] + [delT172]4
F8063FSerbianNN0.2EDNNMPND7.89.17.6NAKT, functional[c.3478C>T] + [c.3478C>T][R1160X] + [R1160X]4
F10173MGermanN0.0NNFailure to thriveMSND9.310.59.3NAKT, functional[c.1258T>G] + [c.121 + 122delCT][F420V] + [L41fsX90] (“Fin major”)1 + 5
F10933FTurkishY0.1ED, pallorPrematurity, apnoe-bradykardia-syndrome, anaemiaCNFNDNANANA3.2No ESRD[c.2014G>C] + [c.2014G>C][A672P] + [A672P]1
F1296 II-13FGermanY0.1EDConnatal CMV infection, occipital aplasia cutis with bone defectNDNDNANANA1.5No ESRD[c.2617delTCAinsCC] + [c.2617delTCAinsCC] + NPHS2: [c.686G>A][F873fsX904] + [F873fsX904] + NPHS2: [R229Q]2 + 3
F1328 II-13MGermanY0.0EDMental retardation, hypertensionFSGSSR; ACE-INANANA25.2No ESRD[c.385C>T] + [c.1868G>T][L129F] + [C623F]1 + 4
F1328 II-33FGermanY0.0EDNFND; ACE-INANANA21.2No ESRD[c.385C>T] + [c.1868G>T][L129F] + [C623F]1 + 4
A229MTurkishN0.2EDNDNDNNNNNNNN?[c.1001T>C] + [c.1001T>C][L334P] + [L334P]13 + 13
A650 II-1MSerbianN0.0EDHydrocephalus, CNS hemorrhage, low birth weightCNFNDDeceased[c.614 + 621delCACCCCGGinsTT] + [c.614 + 621delCACCCCGGinsTT][T205+R207delinsI] + [T205+R207delinsI]4
A797FGermanN0.0Neonatal SP, PUNDNNNANANA0.4No ESRD[IVS27 + 1G>T] + [c.637C>T] + NPHS2: [c.686G>A][Splice-site mutation] + [Q213X] + NPHS2: [R229Q]2 + 13 + 3
A1028MGermanN0.1PU, HT, EDThrombophiliaNDNDNANANA0.7No ESRD[c.1248 + 1249insA] + [c.2607 + 2608insCC][T417fsX418] + [N870fsX905]13 + 13
    NPHS2
F236 II-22MGermanN0.1Acute ED, PUNNFSGSSR9.410.39.4NAKT, functional[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
F355 II-11, 2MGermanN0.0PU, HTNNFSGSSR; CSA: NR9.89.99.8NAKT, functional[c.460 + 461insT] + [c.413G>A][F155fsX167] + [R138Q]3 + 6
F355 II-21, 2FGermanN0.1PUDual aortic archFSGSND6.67.26.5NAKT, functional[c.460 + 461insT] + [c.413G>A][F155fsX167] + [R138Q]3 + 6
F363FItalianNN0.0NNNNNDNNNNNNNNNNNN[c.417 + 418delG] + [c.417 + 418delG][L139fsX181] + [L139fsX181]6
F515 II-12MCzechN0.0EDMental retardationNCGPSR7.37.87.3NAKT, functional[c.413G>A] + [c.417 + 418delG][R138Q] + [L139fsX181]6 + 6
F515 II-22FCzechN0.0PUCNFSR1014.510NAKT, functional[c.413G>A] + [c.417 + 418delG][R138Q] + [L139fsX181]6 + 6
F8592MGermanNN0.0PU, EDNNMCNS >> FSGSSR; CSA: NR7.2NA7.2NAESRD, no KT[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
F876MGermanN0.0EDFSGSNDNANANA4.1No ESRD[c.378G>T] + [c.378G>T][K126N] + [K126N]7
F9352MGermanN0.0EDNNminPGNSRNNNNNNNNNN[c.460 + 461insT] + [c.506T>C][F155fsX167] + [L169P]3 + 7
F942 II-12MGermanN0.1EDHypospadiaFSGS>> FGGSNDNNNNNNNNNN[c.413G>A] + [c.503G>A][R138Q] + [R168H]6 + 7, 8
F942 II-22MGermanN0.1EDHypospadiaNDNDNNNNNNNNNN[c.413G>A] + [c.503G>A][R138Q] + [R168H]6 + 7, 8
F10282MGermanN0.0Diagnosis intrauterine, acute EDNNMPGNNDNANANA9.5No ESRD[c.353C>T] + [c.413G>A][P118L] + [R138Q]7, 8 + 6
F12212MGermanN0.0ED, PUSmall statureFSGSND6.26.76.2NAKT, relapse/failure[c.378G>T] + [c.948delT][K126N] + [P316fsX347]7 + 7
F12332FGermanN0.0PU, HUFailure to thriveATGPSRNANANA2.9No ESRD[c.413G>A] + [c.460 + 461insT][R138Q] + [F155fsX166]6 + 3
F1388FGermanN0.1PUUrinary tract infectionNDNDNANANA0.8No ESRD[c.275G>A] + [c.413G>A][G92D] + [R138Q]13 + 6
A159MCzechN0.2Micro-HUFSGSSRNANANA1.8No ESRD[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
A237 II-1FCzechY0.0SPCNFSR; CP: NR4.35.34.3NAKT, functional[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
A237 II-2FCzechY0.0PU, HUNDNDNANANA3.8No ESRD[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
A248MGermanN0.2PUMCNSSRNNNNNNNNN[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
A356MGermanN0.0Micro-HU, PU, HTNDSRNNNNNNNNN[c.412C>T] + [c.413G>A][R138X] + [R138Q]6 + 6
A674FGermanN0.2ED, HTFailure to thriveMCNS >> FSGSSR; CSA: CR5.86.55.8NAKT, relapse/failure[c.413G>A] +[IVS4 + 1G>T][R138Q] + [Splice-site mutation]6 + 3
A887FGermanN0.0EDCraniofacial dysplasiaNDNNNANANA0No ESRD[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
    WT1 and LAMB2
F1012 II-1FTurkishY0.2ED, HTFSGSNDDeceasedLAMB2: [c.737G>A] + [c.737G>A]LAMB2: [R246Q] + [R246Q]9
F1012 II-2MTurkishY0.0NSNNNNNANANA3No ESRDLAMB2: [c.737G>A] + [c.737G>A]LAMB2: [R246Q] + [R246Q]9
F1234 II-2MGermanN0.0NSEye anomalies, no mental retardationNNNNNANANA0.8No ESRDLAMB2: [c.961T>C] + [c.4177C>T]LAMB2: [C321R] + [L1393F]9
A651FSerbianN0.0EDDMSNNDeceasedWT1: [c.1097G>A]Ex8: [R366H]10
    Single sequence variant
F920FGermanN0.0EDFSGSSS: PR; CP: PR; CSA: PRNANANA15.4No ESRDNPHS2: [c.686G>A] + [?]NPHS2: [R229Q] + [?]3
A816MItalianN0.0EDDeafness, cerebral palsyPDTNN0.81.70NAKT, functionalNPHS1: [c.3478C>T] + [?]NPHS1: [R1160X] + [?]4
A683MTurkishY0.0EDDeafness, unilateral opticusatrophy, mental retardation, pulmonary valve stenosis, recurrence paresisMSNN1.851.8NAKT, relapse/failureNPHS1: [c.3478C>T] + [?]NPHS1: [R1160X] + [?]4
A917FTurkishY0.1ED, hypothyroid.StrabismFGGSNNNANANA2.3No ESRDNPHS1: IVS4 + 2T>G + [?]NPHS1: [splice-site mutation] + [?]13
     No mutation
A163 II-1MTurkishY0.1EDCNSNDDeceasedNo mutationNo mutation
F1373MGermanN0.3EDKidney cysts, mental retardationFSGSSR; CP:NR; CSA:NR17.4NA16.9NAESRD, no KTNo mutationNo mutation
A1018MTurkishNN0.0ED, dystrophyFailure to thriveCNFSR; CP:NR; CSA:NRNANANA0.1No ESRDNo mutationNo mutation
Infantile nephrotic syndrome
F1033MGermanN0.4Enteritis, EDNDNDNANANA3.2No ESRD[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
F398 II-31FGermanN0.6EDNNMCNS >> FSGSSR,CSA: NR4.253.7NAKT, functional[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
F1030FSwissN0.7EDNNFSGSSR, CP: NR1013.1 / 19.19.3NAKT, relapse/failure[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
F1139FGermanNN0.7PU, erythrocyturia, HTNNFSGSSR, CP: NR44.42.8NAKT, functional[c.948del T] + [c.948del T][P316fsX347] + [P316fsX347]7
A126MGermanNN0.8ED, HTShort stature, vesico-urethral refluxFSGSSR6.47.85.7NAKT, relapse/failure[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
A900FGermanN0.8UTI -> PUNeurofibromatosis type I (suspected)MCNSSR, CP: NR?[c.G686A] + [c.1030 + 1031delT][R229Q] + [F343fsX347]3 + 13
F1336FTurkishY0.9ED, HTCMV infectionMCNSSRNANANA0.8No ESRD[c.G868A] + [c.G868A][V290M] + [V290M]3
F260 II-22MGermanNN1.0ED, HTNNSR, CP: NR88.57.0NAKT, functional[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
F1023MGermanNN1.0EDFSGSSR, CSA:NR79.36.0NAKT, relapse/failure[c.413G>A] + [c.460 + 461insT][R138Q] + [F155fsX166]6 + 3
F10452MTurkishNN1.0NNFailure to thriveFSGSSR, CSA:NR8.3NA9.0NAESRD, no KT[c.460 + 461insT] + [c.460 + 461insT][F155fsX166] + [F155fsX166]3
F1305FGermanN1.0NNFSGSSR4.26.33.0NAKT, functional[c.413G>A] + [c.413G>A][R138Q] + [R138Q]6
A28 II-2MTurkishY1.0PUMCNSSR, CP:NRNANANA2.6No ESRD[c.460 + 461insT] + [c.460 + 461insT][F155fsX166] + [F155fsX166]3
    WT1 and LAMB2
A794FAustriaN1.0ED, HT, hyperuricemiaDMSNDNANANA0No ESRDWT1: [c.709G>C]WT1: [E237Q]11
A1021FGermanN0.5EDNDNNNANANA0No ESRDWT1: [c.1180C>G]WT1: [R394P]12
F1234 II-1FGermanN0.3EDEye anomalies, no mental retardationMCNSNDNANANA2.9No ESRDLAMB2: [c.961T>C] + [c.4177C>T]LAMB2: [C321R] + [L1393F]9
     Single sequence variant
F1313FGermanN0.3ED, metabolic acidosis, seizureFailure to thrive, mental retardationMCNSSS: PR; CSA: PRNANANA0.1No ESRDNPHS1: [c.791C>G] + [?]NPHS1: [P264R] + [?]13
A276MHungaryN0.4EDFSGSSRNANANA1.6No ESRDNPHS2: [c.686G>A] + [?]NPHS2: [R229Q] + [?]3
A90MTurkishN0.8EDMPGNSSNANANA3.3No ESRDNPHS2: [c.686G>A] + [?]NPHS2: [R229Q] + [?]3
    No mutation
A63MTurkishY0.4EDNephrocalcinosis, acidosis, facial dysmorphiaNDND0.4NA0NAKT, functionalNo mutationNo mutation
A162MTurkishN0.4ED, HTNNCNSNDNANANA4No ESRDNo mutationNo mutation
F458MItalyNN1.0Failure to thriveFailure to thrive, mental retardationFSGSSRNANANA6.8?No mutationNo mutation
F1224MSerbiaN1.0Acute: EDNNMHCSS-SR, CP: NR, CSA: NRNANANA9.3No ESRDNo mutationNo mutation
F331FTurkishY0.5ED, ascites, HTNNFSGSNN0.7NA0.2NADeceasedNo mutationNo mutation
F1396MGermanY0.5ED, HTNNFSGSNNNNNNNNNN?No mutationNo mutation
F1068FTurkishY0.6EDNNFSGSSS: PR, CP: NNNNNNNNNN?No mutationNo mutation
F287FTurkishN0.6Urine analysisNNFSGSSR,CP: NR, CSA: NRNANANA3.3No ESRDNo mutationNo mutation
F1368MGermanN0.7ED, HTNNFSGSSR, CT: NR2.311.71.5NAKT, functionalNo mutationNo mutation
F1384FGermanNN0.8EDNNNDSS: PRNANANA0No ESRDNo mutationNo mutation
A1006MGermanN0.8EDNNNNNNNANANA0.3No ESRDNo mutationNo mutation
F247 II-2FGermanN1.0NNFSGSSRNANANA0.4DeceasedNo mutationNo mutation
F1074FTurkishNN1.0EDNNFSGSSRNANANA0No ESRDNo mutationNo mutation
A913MEnglandN1.0EDblindnessDMSNNNN12.611.6NAKT, functionalNo mutationNo mutation
A804 IV-6MEnglandN1.0ED, HTNNMGNSRNANANA0.5No ESRDNo mutationNo mutation
A1002MTurkishN1.0EDFoot malformationFSGSSR, CSA: NR1.565NAKT, functionalNo mutationNo mutation
F445 II-1MTurkishY1.0ED, anuriaNNNNSS-SRNANANA17.1No ESRDNo mutationNo mutation
  • References to patients include: (1) Karle S, Uetz B, Ronner V, et al. J Am Soc Nephrol. 2002;13:388–393; (2) Ruf RG, Lichtenberger A, Karle SM, et al. J Am Soc Nephrol. 2004;15:722–732; (3) Schultheiss M, Ruf RG, Mucha BE, et al. Pediatr Nephrol. 2004;19:1340–1348; (4) Mucha B, Ozaltin F, Hinkes BG, et al. Pediatr Res. 2006;59:325–331; and (5) Hasselbacher K, Wiggins RC, Matejas V, et al. Kidney Int. 2006;70;1008–1012. References to mutations include: (1) Schultheiss M, Ruf RG, Mucha BE, et al. Pediatr Nephrol. 2004;19:1340–1348; (2) Beltcheva O, Martin P, Lenkkeri U, Tryggvason K. Hum Mut. 2001;17:368–373; (3) Karle S, Uetz B, Ronner V, et al. J Am Soc Nephrol. 2002;13:388–393; (4) Lenkkeri U, Mannikko M, McCready P, et al. Am J Hum Genet. 1999;64:51–61; (5) Kestila M, Lenkkeri U, Mannikko M, et al. Mol Cell. 1998;1:575–582; (6) Boute N, Gribouval O, Roselli S, et al. Nat Genet. 2000;24:349–354; (7) Ruf RG, Lichtenberger A, Karle SM, et al. J Am Soc Nephrol. 2004;15:722–732; (8) Weber S, Gribouval O, Esquivel EL, et al. Kidney Int. 2004;66:571–579; (9) Hasselbacher K, Wiggins RC, Matejas V, et al. Kidney Int. 2006;70;1008–1012; (10) Royer-Pokora B, Beier M, Henzler M, et al. Am J Med Genet A. 2004;127:249–257; (11) Schumacher V, Scharer K, Wuhl E, et al. Kidney Int. 1998;53:1594–1600; (12) Breuning W, Bardeesy N, Silverman BL, et al. Nat Genet. 1992;1:144–148; (13) this study. ED indicates edema; HT, hypertension; HU, hematuria; NS, nephrotic syndrome; PU, proteinuria; SGA, small for gestational age; SP, sepsis; ACE-I, angiotensin-converting enzyme inhibitor; CR, complete response; CSA, Cyclosporine A; CP, Cyclophosphamide; NEC, nephrectomy; ND, not done; NN, not known; KT, kidney transplant; NR, no response; PR, partial response; SR, steroid resistant; SS, steroid sensitive; ATGP, Alport type glomerulopathy; CNF, Finnish type nephrotic syndrome; DMS, diffuse mesangial sclerosis; FGGS, focal global glomerulosclerosis; FSGS, focal segmental glomerulosclerosis; MCNS, minimal change nephrotic syndrome; MGN, membranous glomerulosclerosis; MHC, mesangial hypercellularity; MPGN, mesangio-proliferative glomerulosclerosis; MS, mesangial sclerosis; minPGN, minimal proliferative glomerulosclerosis; MPCGP, mesangial proliferative crescentic GN; MP, mesangial proliferation; NCGP, nonclassifiable glomerulopathy; NF, no findings; PDT, proliferation of distal tubulus; NN-ND, not known/not done; NN, not known; NA, not applicable; —, not calculated.