TABLE 1.
Clinical and genetic data of 10 families with dRTA and mutations in known dRTA genes.
| Gene Family - Individual | Nucleotide change | Amino acid change | Exon (zygosity, segregation) | PPH2 score | SIFT | Mut taster | Amino acid conservation to species | Gnomad allele frequencies (hom/hemi/het/wt) | Mutation reported in Reference | ACMG classification | Gender | Ethnic origin | Parental consanguinity | Age of onset, yrs | Acidosis | Hypokalemia | Urine pH >5.5 under acidosis | Hypercalciuria | Nephro-Calcinosis | Deafness | T reatment |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ATP6V0A4, ATPase H+ Transporting V0 Subunit A4 (NM_020632.2) | |||||||||||||||||||||
| F589 -22 |
c.2446A>G | p.Lys816Glu | 23 (hom, m,p) | 0.999 | Del | Dis | S. cerevisiae | not reported | novel | likely pathogenic | F | Turkey | Yes | 2 | Yes | Yes | Yes | Yes | Yes | No | NaHCO3, KHCO3 |
| B964 -21 |
c.1346G>A | p.Arg449His | 15 (hom) | 1 | Del | Dis | S. cerevisiae | 0/0/3/246,228 | 62 | likely pathogenic | F | n/a | Yes | <1 | Yes | Yes | Yes | Yes | Yes | No | K-Citrate, NaHCO3 |
| B1673 -21 -22 |
c.1312_1315 del | p.Asp438 Metfs*13 | 14 (hom) | n/a | n/a | n/a | n/a | not reported | 63 | pathogenic | F F |
Serbia Serbia |
No No |
n/d n/d |
Yes Yes |
Yes Yes |
Yes Yes |
Yes Yes |
Stones Stones |
Yes Yes |
K/Na-Citrate, KHCO3 |
| ATP6V1B1, ATPase H+ Transporting V1 Subunit B1 (NM_001692.3) | |||||||||||||||||||||
| F391 -21 |
c.1037C>G | p.Pro346Arg | 10 (hom, m, p) | 1 | Del | Dis | S. cerevisiae | 0/0/4/245,492 | 4 | pathogenic | F | Germany (Turkish) | Yes | <1 | Yes | Yes | Yes | n/a | Yes | Yes | NaHCO3, KHCO3 |
| F608 -21 |
c.497del | p.Thr166 Argfs*9 | 6 (hom) | n/a | n/a | n/a | n/a | 0/0/2/246,220 | 4 | pathogenic | F | Jordan | No | 6 | Yes | Yes | n/d | n/d | Yes | Yes | NaHCO3, KHCO3 |
| F769 -21 |
c.242T>C | p.Leu81Pro | 3 (hom, m, p) | 1 | Del | Dis | S. cerevisiae | 0/0/1/245,488 | 4 | pathogenic | F | Switzerland | No | <1 | Yes | n/d | Yes | n/d | Yes | Yes | NaHCO3, K- Citrate |
| B1459 -21 |
c.1037C>G | p.Pro346Arg | 10 (hom) | 1 | Del | Dis | S. cerevisiae | 0/0/4/245,492 | 4 | pathogenic | F | Yemen | No | <1 | Yes | Yes | n/d | Yes | Yes | Yes | K-Citrate |
| SLC4A1, Solute Carrier Family 4 Member 1 (NM_000342.2) | |||||||||||||||||||||
| F1049 -21 |
c.1766G>A | p.Arg589His | 14 (het) | 0.996 | Del | Dis | C. intestinalis | not reported | 5 | pathogenic | F | Switzerland (Turkish) | n/a | 2 | Yes | n/d | Yes | n/d | Yes | No | K/Na-Citrate |
| B3155 -21 |
c.2573C>A c.1199_1225del |
p.Ala858Asp p.Ala400_Ala408del |
19 (het) 11 (het) |
0.774 n/a |
Del n/a |
Dis n/a |
D. melanogaster | 0/0/17/245,910 0/0/13/282,788 |
64 | pathogenic pathogenic |
F | Malaysia | Yes | 3 | Yes | n/d | n/d | n/d | Yes | No | NaHCO3 |
| B2838 -21 |
c.2573C>A | p.Ala858Asp | 19 (hom) | 0.774 | Del | Dis | D. melanogaster | 0/0/17/245,910 | 64 | pathogenic | F | Pakistani | Yes | n/d | Yes | No | Yes | Yes | Yes | No | K/Na-Citrate |
Del, deleterious; Dis, disease-causing; hemi, hemizygous; het, heterozygous; hom, homozygous; m, maternal; mo., months; n/d, no data; p, paternal; PPH2 score, humvar PolyPhen2 prediction score; SIFT, Sorting intolerant from tolerant; tol, tolerated; VUS, variant of unknown significance; wt, wildtype; yrs, years.