Table 1.

Genotypes and phenotypes of novel mutations in NPHS1, NPHS2, PLCE1, WT1, and LAMB2 detected by high-throughput sequencing in 16 of 48 families with steroid-resistant nephrotic syndrome

Family-IndividualSexEthnic OriginParental ConsanguinityAge of OnsetExtrarenal ManifestationsBiopsy (at Age)Therapy and ResponseNucleotide AlterationAmino Acid ChangeExon (Zygosity, Segregation)Reference (Biobase)Mutationtaster ResultPolyphen Prediction ScoreaContinuous Amino Acid Conservation to SpeciesEVS Allele Frequencies in EA
NPHS1
 A4701–21MUnited States (Hispanic)N3 moFD, Ebstein anomaly, ambiguous genitaliaFSGS (4 mo)ACE-Ic.1223 G>Ap.Arg408Gln10 (het, p)(31, 46)DC1.00Danio rerioA=545/G=8055
LF, hypothyreoismc.2173G>Ap.Glu725Lys16 (het, m)NovelDC1.00D. rerioNREP
 A4715–21MIndiaN2 moNoneNDSteroidsc.1099C>Tp.Arg367Cys9 (hom)(46, 47)PMP1.00M. musculusA=1/C=8599
 A4725–21FIndiaN9 d NoneNDNDc.1099C>Tp.Arg367Cys9 (hom)(46, 47)PMP1.00M. musculusA=1/C=8599
 A4836–21FSaudi ArabiaN1 moNoneNDNDc.2600G>Ap.Gly867Asp19 (hom)(48)DC0.998D. rerioNREP
 A4847–22MIndiaN2 moNoneNDNDc.2600G>Ap.Gly867Asp19 (hom)(48)DC0.998D. rerioNREP
 A4848–22MIndiaN2 moNoneNDNDc.2417C>Ap.Ala806Asp18 (hom)(46, 47)DC1.00D. rerioNREP
 A4863–23FEgyptY5 moNoneNDSRc.3478C>Tp.Arg1160*27 (hom)(46)NANANANREP
 A4913–21MUnited States (Caucasian)N37 yrNoneFSGS (40 yr)SR, CPA, CSA-NRc.2928G>Tp.Arg976Ser22 (hom)(47, 49)DC1.00D. rerioNREP
NPHS2
 A4603–21FEgyptN2 yrFDMPGNSR, CPA-NRc.419delGp.Gly140Aspfs*413 (hom)(10)NANANANREP
WT1
 A4844–21FSerbiaN3 moWT bilateral, GRWT(8 mo)Chemotherapyc.1268G>Ap.Cys423Tyr8 (het)(50)DC0.9D. rerioNREP
 A1399–21FSerbiaN1 yrNoneFSGS (8 yr)Tacrolimusc.1432+5G>TSplice+59 (het)(51)NANANANREP
PLCE1
 A4654–21FUnited States (Arabic)Y4 yrNoneFSGS (4 yr)ACE-Ic.4207A>Tp.Ile1403Phe16 (hom, p, m)NovelDC1.00S. cerevisiaeNREP
 A4682–22MEgyptY4 mononeMPGN (6 mo)Deceasedc.4610T>Gp.Leu1537Arg19 (hom)NovelDC1.00D. rerioNREP
 A4709–23FEgyptY10 moNoneNDNDc.1864C>Tp.Arg622*5 (het)NovelNANANANREP
c.5951–5953delACAp.Asn1984del27 (het)NovelNANANANREP
 A4939–23FEgyptY1 yrNoneNDSRc.5951–5953delACAp.Asn1984del27 (hom)NovelNANANANREP
LAMB2
 A4938–25FSaudi ArabiaY1 mononeNDNDc.253delGp.Glu85Lysfs*273 (hom, p, m)NovelNANANANREP
  • EVS, Exome Variant Server; EA, European American; M, male; N, no; ACE-I, angiotensin-converting enzyme inhibitor; het, heterozygous; p, paternal; DC, disease-causing; FD, facial dysmorphia; LF, liver fibrosis; m, maternal; ND, no data; hom, homozygous; NREP, not reported; PMP, polymorphism; F, female; Y, yes; NA, not applicable; SR, steroid-resistant; CPA, cyclophosphamide; CSA, cyclosporine A; NR, no response; MPGN, membranous glomerulosclerosis; WT, Wilms' tumor; GR, growth retardation; D. rerio, Danio rerio; M. musculus, Mus musculus; S. cerevisiae, Saccharomyces cerevisiae.

  • a Polyphen prediction score ranges from 0 to 1.0; 0=benign, 1.0=probably damaging.