Table 1. Mutations of FAT1 in four families with nephrotic syndrome (NS) and tubular ectasia (TE).
| Family-Individual | Sex | Ethnic origin | Nucleotide change | Amino-acid change | Exon (zygosity, segregation) | MT | PP2* | Amino-acid conservation | Frequencies in the EVS database† | Frequencies in the dbSNP database‡ | Consanguinity | Age of onset (age at ESRD) | Renal manifestation | Extrarenal manifestations | Biopsy (at age) | Therapy and response |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A4623 | M | Turkish | c.3093_3096del | p.P1032Cfs*11 | 2 (Hom) | NA | NA | — | — | — | Yes | 15 years | NS, TE, HU | ID, PMG, BP, PAS | TIN, MS, thin GBM (12 years) | — |
| A3027 | M | Arab | c.857A>G | p.N286S | 2 (Hom) | DC | 0.016 | D.r. | — | rs201488687 MAF=0.0002 | Yes | 15 years (15 years) | NS, TE, HU | Ewing sarcoma (15 years) with lung and spinal metastasis, RVUR IIIo | ND | HD, RT, CHT, deceased at 19 years |
| A789 | F | African-American | c.3008C>Tc.9259C>T | p.A1003Vp.R3087G | 2 (het)13 (het) | DCDC | 10.999 | C.e.C.e. | AA=0/AG=1/GG=6110AA=0/AG=1/GG=6,164 | rs369363545 (MAF, N/A)rs375998390 (MAF, N/A) | No | 9 years | NS, TE, HU | Hodgkin lymphoma (10 years) | MCNS (9 years) | SR, CsA, CHT |
| A3507 | F | African | c.4517G>Ac.5671C>A | p.R1506Hp.P1891T | 8 (het)10 (het) | DCDC | 0.4941.0 | C.e.C.e. | —TT=0/TG=2/GG=6,048 | —rs185078412MAF=0.0006 | No | 2 months | NS, TE, HU | Hydrocephalus | DMS (2 years) | Unilateral NE (2 years) |
BP, Bilateral blepharoptosis; C.e., Caenorhabditis elegans; CHT, chemotherapy; CsA, cyclosporin A; DC, disease causing; DMS, diffuse mesangial sclerosis; D.r., Danio rerio; ESRD, end-stage renal disease; EVS, Exome Variant Server; F, female; FSGS, focal segmental glomerulosclerosis; GBM, glomerular basement membrane; HD, haemodialysis; het, heterozygous; Hom, homozygous; HU, haematuria, ID, Intellectual disability; m, Maternal; M, male; MCNS, minimal change nephrotic syndrome; mo, month; MS, mesangial sclerosis; MT, mutationtaster; N, no; NA, not applicable; N/A, not available; NE, nephrectomy; ND, no data; p, paternal; PAS, pulmonary artery stenosis; PMG, pachygyria; PP2, Polyphen Prediction score Humvar; RT, radiotherapy; RVUR, right vesicourethral reflux; SR, steroid resistant; TE, tubular ectasia; TIN, tubular interstitial nephritis; Y, yes.
*Polyphen prediction score HumVar ranges from 0 to 1.0. 0, benign; 1.0, probably damaging.
†Exome variant Server (http://evs.gs.washington.edu/EVS/).
‡dbSNP database (http://www.ncbi.nlm.nih.gov/SNP).