Table 1.
Clinical and genetic details of likely resolved families
| Gene | Pedigree ID | Allele 1a | Allele 2a | Ethnicityb (sex) | Age at first stone | No. stonesc | Stone compd | ESKD (E) or eGFR, agee | NCf | U/Cag | hU/Ox | U/pHi | U/Citj | Commentsk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Biallelic |
||||||||||||||
| AGXT | PHN244 | c.(1_358del) (p.Met1fs) | c.(1_358del) (p.Met1fs) | White (F) | 3 yr | 3 | CaOx | 110, 10 yr | N | 57 | 114 | 7.0 | 529 | Parents confirmed heterozygous carriers |
| APRT | PHN201 | c.3G>C (p.Met1?) | c.3G>C (p.Met1?) | So Asian (F) | NA | Mult | NA | E, 45 yr | Y, 45y | Anuric | Anuric | Anuric | Anuric | |
| PHN2-1 | c.81-3C>G (p.Asp28?) | c.81-3C>G (p.Asp28?) | White (M) | NA | 2 | NA | E, 51 yr | Y, 51y | Anuric | Anuric | 6.5 | Anuric | Very low APRT, blood spot assay | |
| PHN2-2 | c.81-3C>G (p.Asp28?) | c.81-3C>G (p.Asp28?) | White (M) | - | 0 | - | E, 50 yr | N | Anuric | Anuric | Anuric | Anuric | Crystals on biopsy | |
| ATP6V1B1 | DDN55 | c.1037C>G (p.Pro346Arg) | c.1037C>G (p.Pro346Arg) | Mid East (F) | 2 mo | Mult | CaOx, AP | 35, 9 mo | Y, 6m | 1081 | 286 | 7.5 - 8 | NA | Sensorineural deafness, 7 mo |
| CLDN16 | PHN193 | c.293G>A (p.Cys98Tyr) | c.293G>A (p.Cys98Tyr) | So Asian (M) | - | 0 | - | E, 34 yr | Y, 34y | NA | 12.5 | NA | NA | |
| PHN87 | c.338G>T (p.Cys113Phe) | c.338G>T (p.Cys113Phe) | So Asian (M) | 6 mo | Mult | CaOx | E, 17 yr | Y, 17y | 190 mg/g | 128 | NA | NA | Hypocalcemic tetany, seizures, deafness | |
| PHN208 | c.359G>A (p.Cys120Tyr) | c.359G>A (p.Cys120Tyr) | Hispanic (M) | - | 0 | - | NA | Y, 6y | 5.5 | 74.3 | NA | 315 | Parapelvic renal cysts | |
| PHN13 | c.427+5G>A (p.Leu143?) | c.427+5G>A (p.Leu143?) | SE Asian (M) | 13 yr | Mult | NA | E, 21 yr | N | 234 mg/24 h | 37 mg/24 hr | NA | NA | ||
| PHN38 | c.445C>T (p.Arg149*) | c.445C>T (p.Arg149*) | Mid East (M) | NA | NA | NA | NA | NA | NA | 57 | NA | NA | ||
| PHN223 | c.445C>T (p.Arg149*) | c.445C>T (p.Arg149*) | Mid East (F) | 16 yr | NA | NA | NA | Y, 16y | NA | NA | NA | NA | ||
| PHN226 | c.571G>A (p.Gly191Arg) | c.571G>A (p.Gly191Arg) | Mid East (F) | 1.5 yr | NA | NA | NA | Y, 4y | NA | NA | NA | NA | ||
| DDN28 | c.646C>T (p.Arg216Cys) | c.646C>T (p.Arg216Cys) | So Asian (M) | NA | NA | NA | E, 2 yr | Y, 2y | 486 mg/24 h | 126 | 6 | NA | SLC4A1: p.Glu906Gln | |
| CLDN19 | DDN60 | c.392T>G (p.Leu131Arg) | c.392T>G (p.Leu131Arg) | AA (M) | - | 0 | - | 83, 11 yr | Y, 11y | NA | NA | 7 | NA | Rickets, eye glasses, 11 yr |
| PHN112 | c.535G>A (p.Gly179Ser) | c.535G>A (p.Gly179Ser) | So Asian (M) | 2 yr | Mult | CaOx | E, 16 yr | Y, 16y | NA | 3.1 mg/24 h | NA | NA | High myopia | |
| CYP24A1 | PHN10 | c.364G>T (p.Glu122*) | c.1226T>C (p.Leu409Ser) | White (M) | - | 0 | - | 91, 4 yr | Y, 1y | 4.8 | 89 | 7 | 189 | |
| PHN42 | c.428_430del (p.Glu143del) | c.1186C>T (p.Arg396Trp) | White (M) | 17 yr | NA | NA | 80, 17 yr | Y, 16y | 288 | 83 | 7 | 416 | Proven biallelic, BRC | |
| PHN28 | c.1226T>C (p.Leu409Ser) | c.1226T>C (p.Leu409Ser) | White (M) | 36 yr | 1 | CaOx | E, 43 yr | Y, 36y | 369 | 40.5 | 5.7 | 329 | ||
| GRHPR | PH2-6 | c.864_865delTG (p.Val289fs20*) | c.214_493del (p.Gly72fs) | Chinese (F) | 17 yr | 3 | CaOx | E, 28 yr | NA | Anuric | Anuric | Anuric | Anuric | |
| KCNJ1 | PHN213 | c.562C>A (p.Arg188Ser) | c.562C>A (p.Arg188Ser) | White (F) | NA | NA | NA | 173, 11 yr | Y, 11y | 445 mg/g | 37 mg/g | 7.1 | 898 | BSND: p.Gly304Arg |
| DDN36 | c.1058dupC (p.His354Serfs) | c.788T>G (p.Ile263Ser) | White (M) | 57 yr | NA | CaOx | 32, 59 yr | Y, 58y | 178 | 40 | 6.2 | 261 | ||
| SLC12A1 | DDN13 | c.769G>A (p.Gly257Ser) | c.1424G>A (p.Cys475Tyr) | White (M) | 3 yr | NA | NA | 83, 3 yr | Y, 3y | 6.5 | 78mg/g | 7 | 212mg/g | |
| SLC34A1 | PHN233 | c.1466A>G (p.Tyr489Cys) | c.1466A>G (p.Tyr489Cys) | Icelandic (F) | NA | NA | NA | 110, 7 yr | Y, 4y | 605mg/g | 356mg/g | NA | 202 | MSK |
| SLC34A3 | DDN6 | c.413C>T# (p.Ser138Phe) | c.448+1G>A (p.Lys149?) | White (F) | 17 yr | Mult | COD/COM | 38, 19 yr | Y, 17y | 233 | 55 | 6.4 | 127 | |
| c.1576_1578del# (p.Leu527del) | ||||||||||||||
| DDN39 | c.560+23_561-42del (p.Arg187?) | c.1058G>T (p.Arg353Leu) | White (F) | 16 yr | 1 | NA | 61, 18 yr | Y, 16y | 342 mg | NA | NA | NA | ||
| DDN33 | c.1247delT (p.Leu416Profs) | c.1247delT (p.Leu416Profs) | SE Asian (M) | 8 yr | Mult | CaOx | 103, 11 yr | Y, 8y | 15.4 | 51 | 5.5-7 | 257-608 | ||
| DDN41 | c.1453C>T (p.Arg485Cys) | c.1454G>A# (p.Arg485His) | White (M) | 16 yr | ∼50 | COD/COM | 101, 37 yr | N | 376 | NA | NA | NA | ||
| c.1585A>T# (p.Ile529Phe) | ||||||||||||||
|
SLC4A1 |
DDN57 |
c.2573C>T (p.Ala858Asp) |
c.2573C>T (p.Ala858Asp) |
Mid East (M) |
NA |
Mult |
AP |
92.5, 7 yr |
Y, 7y |
153 mg/g |
NA |
8.5 |
452 |
|
| Monoallelic | ||||||||||||||
| CASR | PHN31 | c.649G>T (p.Asp217Ty) | ND | African (M) | - | 0 | - | 142, 3 yr | Y, 1y | 12 | 112 | 7.2 | 958 | HS, <1y, congenital HPT; SLC12A1, p.Gly397Asp |
| CYP24A1 | DDN51 | c.469C>T (p.Arg157Trp) | ND | White (F) | 19 yr | 1 | NA | >90, 27 yr | Y, 19y | 339 | 28 | 6.9 | 495 | BRC, SLC34A1: p.Ala133Val, CYP24A1: p.Arg157Gln |
| HNF4A | DDN12 | c.253C>T (p.Arg85Trp) | ND | White (M) | NA | NA | NA | 75, 10 yr | Y, 16y | 8.2 | 59.1 | 7.0 | 1893 | Fanconi, rickets, glucosuria, UP 30, |
| DDN7 | c.253C>T (p.Arg85Trp) | ND | White (M) | NA | NA | NA | 75, 6 yr | Y, 11y | 8.2 | 60.4 | 6.6 | 1168 | Fanconi, severe bone disease, UP 100 | |
| SLC34A1 | DDN61 | c.241dupG (p.Glu81Glyfs) | ND | White (F) | - | 0 | - | 98, 3 yr | Y, 15m | NA | NA | NA | NA | SLC34A1: c.1175-3C>A |
| DDN26 | c.460_480dup (p.Ile154_Val160dup) | ND | Brazil (F) | 7 yr | 4 | NA | 125, 15 yr | Y, 7y | 4.2 | NA | NA | NA | UTI, 7y, RBP slightly high, SLC34A3: c.561-8G>ASLC26A1: c.577-1G>A | |
| SLC34A3 | PHN245 | c.(1-?)_(1797+)del (p.Met1fs) | ND | White (M) | NA | NA | NA | NA | Y, 6y | 3.7 | 100 | 8 | 32 | SLC34A3: c.305-7G>A |
| PHN32 | c.575C>T (p.Ser192Leu) | ND | White (F) | - | 0 | - | NA | Y, 10y | 4.6 | 100 | 7.0 | 558 | ||
| PHN180 | c.575C>T (p.Ser192Leu) | ND | White (M) | 48 y | 3 | NA | 31, 56 yr | N | 118 | 51 | 6.1 | 299 | ||
| PHN239 | c.575C>T (p.Ser192Leu) | ND | White (M) | 35 y | Mult | NA | 42, 62 yr | NA | 84 | 135 | 5.4 | 392 | SLC34A3: p.Pro571SerSLC3A1: c.1136+2T>C | |
| PHN250 | c.575C>T (p.Ser192Leu) | ND | NA (M) | 7 mo | 3 | CaOx | NA | NA | NA | NA | NA | NA | ||
| PHN219 | c.846G>A (p.Pro282?) | ND | White (M) | 4 yr | 2 | NA | NA | NA | 5.2 | 79.5 | 7.0 | 527 | ||
| PHN274 | c.1454G>A# (p.Arg485His) c.1585A>T# (p.Ile529Phe) |
ND | White (F) | <18 yr | Mult. | CaOx | - | Y, 36y | 343 | 120 | >8 | 534 | MSK | |
| PHN156 | c.1246_1247del (p.Leu417Thrfs) | ND | White (M) | 12 yr | 1 | CaOx | 90, 12 yr | Y, 12y | 9.2 | 68 | 7.0 | 488 | Autism | |
| PHN53 | c.1623G>A (p.Trp541*) | ND | White (F) | - | 0 | - | 117, 30 mo | Y, 1y | 8.9 | 74 | 7.0 | 523 | Failure to thrive, 9 mo; CYP24A1, p.Glu143del |
|
| SLC4A1 | PHN152 | c.1765C>T (p.Arg589Cys) | ND | White (M) | - | 0 | - | 150, 6 yr | Y, 6y | 4.3 | 100 | 7.0 | <73 | Urinary incontinence |
| DDN8 | c.2726T>C (p.Met909Thr) | ND | White (M) | - | 0 | - | 81, 6 yr | Y, 5y | 3.1 | 48.9 | 7.4 | <48 | Hematuria, prenatal hydronephrosis | |
| Chr4q del | PHN20 | chr4 (85,553,401-104,356,614) 18.8MB | ND | White (M) | 6 mo | Mult | NA | 139, 6 mo | N | 466 | 399 mg/g | 6 | NA | Failure to thrive |
Biochemical values outside the normal range are shown in boldface type. NA, information not available.
Allele: # = variants suspected of being on the same allele; ND, not detected.
Ethnicity (sex): Mid, middle; So, south; SE, south east; AA, African American; (F), female; (M), male; NA, information not available.
No. stones, total number of stones observed; Multi, multiple.
Stone comp, stone composition; CaOx, calcium oxalate; AP, apatite; COD/COM, calcium oxalate dihydrate/calcium oxalate monohydrate.
ESKD, eGFR, age: E, end-stage kidney disease with age indicated; yr, year; mo, month; estimated glomerular filtration rate (eGFR), value and age indicated; eGFR calculated with Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (ml/min per 1.73 m2) or Full Age Spectrum (FAS) pediatric equation for patients <1 yr.
NC, nephrocalcinosis; Y, yes and age first detected; y, year; m, month; N, no.
U/Ca , urine calcium, shown as mg/24 h when ≥18 yr or as mg/kg per 24 h when <18 yr (underlined), unless otherwise shown.
U/Ox, urine oxalate, shown as mg/24 h when ≥18 yr or as mg/1.73 m2 when <18 yr (underlined), unless otherwise shown.
U/pH, urine pH
U/Cit, urine citrate shown in mg/24 h when >18 yr or as mg/g creatinine when <18 yr (underlined). Creatinine normalization (mg/g creatinine).
Comments: BRC, bilateral renal cysts; RBP, retinol binding protein; HPT, hyperparathyroidism; HS, hypocalcemic seizures; MSK, medullary sponge kidney; UTI, urinary tract infection; UP, urinary protein. Variants that may be significant to the phenotype are shown in boldface type.