Table 1. Recessive mutations in NOS1AP in two families with early-onset NS.
Cr, serum creatinine; DC, disease causing; DL, deleterious; ESRD, end-stage renal disease; ExAC v1.0 and gnomAD v2.11 and v3, summary of data within Exome and Genome Aggregation databases; H, homozygotes in ExAC and gnomAD; h, heterozygous alleles in ExAC and gnomAD; HD, hemodialysis; hom, homozygous; ME, MaxEnt splice prediction score; MT, “MutationTaster” prediction score; N/A, not available; NNS, NNSPLICE splice-site mutation prediction score; PC, parental consanguinity; PD, probably damaging; PP2, PolyPhen-2 prediction score; RUS, renal ultrasound; SGA, small for gestational age; SIFT, “Sorting Tolerant From Intolerant” prediction score; Seg, segregation; T, total alleles in ExAC and gnomAD; TP, total protein; TX, kidney transplantation; Zyg, zygosity.
| Family |
Nucleotide and
amino acid change |
Exon (Zyg and
Seg) |
In silico
severity scores |
Conservation |
ExAC and
gnomAD (H/h/T) |
Sex |
Ethnic
origin |
Renal disease |
| A1018 |
c.428G>A
p.Cys143Tyr |
5 (hom, mat) |
PP2 PD
SIFT DL MT DC |
C. elegans | Absent | M | N/A |
Initial onset:
4 days, SGA, edema Urinalysis: Microscopic hematuria; 18.5 g protein/g creatinine Serum studies: Cr 1.0 mg/dl, TP 4.8 g/dl. RUS: N/A Treatment: Resistant to corticosteroids, cyclophosphamide, and cyclosporin A. Biopsy: 75% podocyte foot effacement. ESRD: 7 years (HD and TX). |
| A5106 |
c.345-3T>G
Splice |
5 (hom) |
ME −66%
NNS −97% |
Not
applicable |
Absent | M | Egypt |
Initial onset:
6 months, edema Urinalysis: Microscopic hematuria; 3 g protein/g creatinine. Serum studies: Cr 0.6 mg/dl, TP 3.8 g/dl, Albumin 2.2 g/dl. RUS: Bilateral echogenicity |