Table 2. Genotypes and phenotypes from patients with SRNS, in whom the causative mutation was identified in one of 24 known monogenic SRNS genes.
Patients are listed in order of age of onset (see Figure 2).
| Patient | Gene | Nucleotide alteration |
Amino acid alteration |
Sex (karyot- ype) |
MOI (zygosity) |
Amino acid conservation to species |
ExAC** | Ethnicity | Age of onset (years) |
Consan- guinity |
Initial biopsy |
Variant Class*** |
Reference (PubMed ID) |
Clinical consequences of finding |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| B144_24 | NPHS1 | c.728C>T | p.P243L | F | AR (Hom) | D. melanogaster | - | Arabic | 0.1 | Yes | ND | Likely Pathogenic | novel | Genetic Counseling; recurrence risk in Tx reduced |
| B350_22 | NPHS1 | c.1868G>T | p.C623F | F | AR (Hom) | D. rerio | 3/0/119,848 | Caucasian | 0.3 | No | DMS | Pathogenic | 9915943; 11726550 | Genetic Counseling; recurrence risk in Tx reduced |
| B9_22 | MYO1E | c.141C>G | p.Y47* | M | AR (Hom) | NA | - | Arabic | 0.8 | Yes | ND | Pathogenic | 23595123 | Genetic Counseling; Recurrence risk in Tx reduced |
| B188_21 | NPHS2 | c.855-56AA>del | p.R286Tfs *17 | F | AR (Hom) | NA | 8/0/115,938 | Hispanic | 3.2 | No | MCNS | Pathogenic | 10742096 | Genetic Counseling; recurrence risk in Tx reduced |
| B323_21 | WT1 | c.1384C>T | p.R462W | F (46,XY) | AD (het) | S. cerevisiae | - | Caucasian | 3.2 | No | FSGS | Pathogenic | 1655284 | Genetic Counseling; recurrence risk in Tx reduced; screening for GB |
| B92_21 | WT1 | c.1432+4C> T | IVS9 C-T +4 KTS | F (46,XY) | AD (het) | NA | - | Caucasian | 4.0 | No | FSGS | Pathogenic | 9398852 | Genetic Counseling; recurrence risk in Tx reduced |
| B635_21 | TRPC6 | c.2683C>T | p.R895C | F | AD (het) | D. rerio | - | Indian | 5.2 | No | ND | Pathogenic | 15924139 | potentially CNI sensitive; recurrence risk in Tx reduced |
| B284_21 | INF2 | c.542T>G | p.V181G | M | AD (het) | H. sapiens | - | Caucasian | 14.3 | No | FSGS | Pathogenic | 23014460 | Genetic Counseling; recurrence risk in Tx reduced |
All probands from each of the families in whom the causative gene was identified are listed above. AR, autosomal recessive; AD, autosomal dominant; CNI, calcineurin inhibitor; DMS, diffuse mesangial sclerosis; F, female sex; fs, frameshift; FSGS; focal segmental glomerulosclerosis; GB, gonadoblastoma; het, heterozygous; Hom, homozygous; KTS, KTS splice site at junction of exon/intron 9; M, male sex; MOI, mode of inheritance; NA, not available; ND, not done; Tx, transplant;
*
truncating;
**
ExAC frequencies reported heterozygotes/homozygotes/total alleles;
-, not present in ExAC.
***
Variants classified as per ACMG guidelines [34]