Table 2.
Molecular genetic diagnoses established in 11 of 143 (7.7%) individuals from 143 families with NL/NC in one of five dominant genes
| Gene [Protein] (Individual with mutation) | Nucleotide Change | Amino Acid Change | Zygosity State | PPh2, Evolutionary Conservation | Reference | Sex | Age of Onset, yr | NL/NC | Stone Analysis | Clinical Diagnosis (Before Mutational Analysis) | Genetic Diagnosis (After Mutational Analysis) | Practical Implication (Following Genetic Diagnosis)a |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ADYC10 [Adenylate cyclase 10 (soluble)] | c.1052C>A | p.Pro351His | het | 1.00, G.g | Novel | M | 15 | NL | CaOx | HC | Absorptive HC | Genetic counseling |
| c.758G>A | p.Cys253Tyr | het | 0.69, M.m. | Novel | M | 1.5 | NL+NC | N/A | HC | Absorptive HC | ||
| (B580)b | ||||||||||||
| (B599)b | ||||||||||||
| SLC4A1 [Anion exchanger (Diego blood group)] (B280)b | c.1766G>A | p.Arg589His | het | 0.95, X.t. | 25 | F | 11 | NC | N/A | dRTA + cysts | Primary dRTA | Monitor for hereditary spherocytosis, osteomalacia, hypokalemia, and periodic paralysis, genetic counseling |
| SLC9A3R1 [NHE3, cation proton antiporter 3] (B529)c | c.328C>G | p.Leu110Val | het | 0.10, M.m. | 27 | F | 11 | NL | N/A | HPh | NPHLOP2 | Monitor bone density, genetic counseling |
| SLC34A1 [Type 2 sodium/phosphate cotransporter] | c.458G>T | p.Gly153Val | het | 1.00, D.r. | Novel | M | 4 | NL | N/A | HPh, idiopathic HC | NPHLOP1/FS | Screen for deafness, genetic counseling |
| c.398C>T | p.Ala133Val | het | 0.99, D.r. | 30 | M | 3 | NL | N/A | HPh, HC | NPHLOP1/FS | ||
| c.437C>T | p.Pro146Leu | het | 0.95, D.r. | Novel | M | 3 | NL | N/A | HPh | NPHLOP1/FS | ||
| c.1367T>A | p.Ile456Asn | het | 0.99, D.r. | Novel | F | 9 | NL | CaOx, CaPh | HSP, HC | NPHLOP1/FS | ||
| c.1348G>A | p.Gly450Ser | het | 0.99, D.r. | Novel | M | 7 | NL | CaOx | HPh, idiopathic HC | NPHLOP1/FS | ||
| (B491)c | ||||||||||||
| (B523)c | ||||||||||||
| (B484)c | ||||||||||||
| (B610)b,d | ||||||||||||
| (B417)c | ||||||||||||
| VDR [Vitamin D (1, 25-dihydroxyvitamin D3) receptor] | c.260A>G | p.Asn87Ser | het | 0.99, D.r. | Novel | M | 12 | NL | N/A | HPh | VDDR2A | Calcium supplements, genetic counseling |
| c.1207G>A | p.Glu403Lys | het | 0.90, D.r. | Novel | F | 4 | NL | N/A | HPh | VDDR2A | ||
| (B481)c | ||||||||||||
| (B447)c |
PPh2, Polyphen2-HumVar (http://genetics.bwh.harvard.edu/pph2/); NL, nephrolithiasis; NC, nephrocalcinosis; het, heterozygous; G.g., Gallus gallus; M, male; CaOx, calcium oxalate; HC, hypercalciuria; M.m., Mus musculus; N/A, not available; X.t., Xenopus tropicalis; F, female; dRTA, distal renal tubular acidosis; HPh, hypophosphatemia; NPHLOP2, hypophosphatemic nephrolithiasis/osteoporosis, 2; D.r., Danio rerio; NPHLOP1, hypophosphatemic nephrolithiasis/osteoporosis, 1; FS, Fanconi syndrome; CaPh, calcium phosphate; HSP, Henoch-Schonlein purpura; VDDR2A, Vitamin D-dependent rickets, type 2A.
Practical implications are based off the defined Online Mendelian Inheritance of Man database phenotype (http://www.omim.org).
Patients are American.
Patients derive from the Balkan region.
B610 is an adopted individual and biologic family information is unavailable.