| Individual / source | Genotype | Clinical facts | Sulfate and oxalate biochemistry | Evidence and uncertainty |
|---|---|---|---|---|
| **A3054-21** — Gee et al., 2016 | **NM_022042.3:** compound heterozygous c.554C>T (p.Thr185Met) and c.1073C>T (p.Ser358Leu) | Male of Macedonian ancestry; onset at **5 years**; recurrent calcium-oxalate nephrolithiasis, nephrocalcinosis, hypocitraturia, bilateral obstructive calculi, bilateral ureteropelvic-junction obstruction, and acute kidney injury (pqac-00000005, pqac-00000016, pqac-00000024) | **Sulfate:** not measured. **Oxalate:** hyperoxaluria reported; stone analyzed as calcium oxalate (pqac-00000005, pqac-00000013) | Both variants reduced sulfate/bicarbonate exchange in vitro. p.Thr185Met caused defective folding, endoplasmic-reticulum retention, and near-absent transport; p.Ser358Leu showed impaired processing/protein stability. The causal role of altered oxalate transport was not directly tested in these assays (pqac-00000006, pqac-00000008, pqac-00000022). |
| **B641-12 (MA-1015)** — Gee et al., 2016 | **NM_022042.3:** homozygous c.166G>A (p.Ala56Thr) | European-American boy born to consanguineous parents; stone detected by CT during evaluation of abdominal pain; renal function normal; paternal grandfather had nephrolithiasis. **Age at onset was not reported** (pqac-00000023, pqac-00000027) | **Sulfate:** not measured. **Oxalate:** 24-hour urinary oxalate within the normal range (pqac-00000023, pqac-00000027) | Variant was rare in the databases available in 2016 and not observed homozygously; mutant protein reached the plasma membrane but had reduced anion-exchange activity. Stone composition is reported as calcium oxalate in the study table, although the narrative provides limited compositional detail (pqac-00000006, pqac-00000024, pqac-00000031). |
| **Index patient** — Pfau et al., 2023 | **NM_022042.4:** homozygous c.824T>C (p.Leu275Pro) | Woman evaluated at **33 years**; more than 6 years of intermittent chest pain with MRI-confirmed bilateral third/fourth costal perichondritis, predominantly right-sided; 13-mm right upper-calyx renal stone; normal kidney function; parents were first cousins (pqac-00000002, pqac-00000004, pqac-00000012) | **Plasma sulfate:** 138–159 μmol/L, mean 148 versus approximately 300 reference. **Sulfate FEI:** 0.20–0.27, mean 0.24—considered inappropriately high during hyposulfatemia. **Urinary oxalate:** 21.8–48.6 mg/day, mean 33.7; plasma oxalate <2 μmol/L (pqac-00000003, pqac-00000064, pqac-00000065) | Oocyte assays demonstrated markedly reduced sulfate and oxalate transport, reduced surface expression, and reduced total protein, supporting loss of function. Renal-stone composition was unavailable; hyperoxaluria was not reproducible, and causation of the perichondritis or stone remains inferential. The authors explicitly stated that evidence did not yet satisfy ClinGen criteria for a defined Mendelian disorder (pqac-00000001, pqac-00000002, pqac-00000018, pqac-00000039). |


*Table: Comparison of the three reported individuals with biallelic SLC26A1 variants, emphasizing genotype, phenotype, sulfate handling, oxalate findings, functional evidence, and major uncertainties.*