TABLE 2.
Clinical and genetic data of 4 families with dRTA with mutations in the novel candidate genes ATP6V1C2, WDR72, and SLC4A2.
| 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 | ACMG classification | Gender | Ethnic origin | Parental consanguinity | Age of onset, yrs | Acidosis pH HCO3 (mmol/L) | Hypo-Kalemia (mmol/L) | Urine pH >5.5 under acidosis | Hypercalciuiria | Nephrocalcinosis | Deafness | Treatment | Comment |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ATP6V1C2, ATPase H+ Transporting V1 Subunit C2 (NM_001039362.1) | ||||||||||||||||||||||
| B1022 -21 |
c.503T>C | p.Ile168Thr | 7 (hom, m, p) | 0.975 | Del | Dis | C. intestinalis | 0/0/224/277222 | novel | likely pathogenic | F | Egypt | Yes | <1 | Yes ph 7.2 HCO3 10 | Yes 1.8 | 8.6 | No | No | No | Polycitrate Potassium | Death age 9 mo due to renal failure |
| WDR72, WD Repeat Domain 72 (NM_182758.3) | ||||||||||||||||||||||
| F382 -25 |
c.477_485dup | p.(Ile159_Cys161dup) | 5 (hom) | n/a | n/a | n/a | n/a | not reported | novel | likely pathogenic | F | Turkey | Yes | 5 | Yes pH 7.1 HCO3 11.5 | Yes 2.5 | 8 | Yes | Yes | No | NaHCO3 KHCO3 | Enamel Defect |
| B2673 -21 -22 |
c.764_768delGGCAG | p.Gly255Val fs*40 | 8 (hom) | n/a | n/a | n/a | n/a | 0/0/1/246104 | novel | pathogenic | F M |
Indian | No | 3 <1 |
Yes 11 Yes 10 |
Yes 2.4 Yes 2.8 |
7 7.5 |
No No |
No No |
Yes n/d |
NaHCO3 KHCO3 | Enamel Defect Enamel Defect |
| SLC4A2, Solute Carrier Family 4 Member 2 (NM_01199692.2) | ||||||||||||||||||||||
| F588 -21 |
c.2107G>A | p.Ala703Thr | 14 (hom, m, p) | 0.995 | Del | Dis | G. gallus | 0/0/1/250904 | novel | VUS | F | Turkey | Yes | 1 | Yes 7.1 | Yes 2.5 | 7 | Yes | Yes | Yes | NaHCO3, KHCO3 | |
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; wt, wildtype; yrs, years.