Table 1.

Molecular genetic diagnoses established in 13 of 143 (9.1%) individuals from 143 families with NL/NC in one of nine recessive or X-linked genes

Gene [Protein] (Individual with Mutation)Nucleotide ChangeAmino Acid ChangeZygosity StatePPh2, Evolutionary ConservationReferenceSexAge of Onset, yrNL/NCStone AnalysisClinical Diagnosis (Before Mutational Analysis)Genetic Diagnosis (After Mutational Analysis)Practical Implication (Following Genetic Diagnosis)a
ATP6V1B1 [ATPase, H+ transporting, lysosomal 56/58 kDa, V1 subunit B1] (B482)bc.242T>Cp.Leu81Prohom1.00, X.t.14M7NLCaOxIncomplete dRTAdRTA, deafnessHearing screen, monitor for ↑ K+, no diagnostics for secondary causes, genetic counseling
ATP6V0A4 [ATPase, H+ transporting, lysosomal V0 subunit a4] (B329)cc.292–1G>Aobligatory splicecomp hetN/ANovelF<1NL+NCN/AHC, HK, dRTA, metabolic acidosisdRTAMonitor for ↑ K+, no diagnostics for secondary causes, genetic counseling
c.1346G>Tp.Arg449Leu1.00, X.t.34
CLDN16 [Claudin 16] (B604)bc.453G>Tp.Leu151Phehom0.99, X.t.17M13NCN/AFHHNCFHHNCMonitor for tetany and seizures, no diagnostics for secondary causes, genetic counseling
CLDN19 [Claudin 19] (A4592)cc.59G>Ap.Gly20Asphom0.99, D.r.18F15NL+NCN/AMedullary NC, HC, HMHOMG5Evaluate for eye disease, monitor for NC, genetic counseling
SLC3A1 [Cystine, dibasic and neutral amino acid transporters, activator of cystine, dibasic, and neutral amino acid transport]c.647C>Tp.Thr216Methom0.98, D.r.35F2NLCystineCystinuria, HOCystinuriaVery high fluid intake, treatment with tiopronin and potassium citrate, alkalinization of urine, limit animal protein intake, genetic counseling
c.647C>Tp.Thr216Methom0.98, D.r.35M1NLCystineCystinuriaCystinuria
c.1094G>Ap.Arg365Glncomp0.94, D.r.36F17NLCystineCystinuriaCystinuria
c.1400T>Cp.Met467Thrhet0.29, D.r.24
 (B425)b
 (B458)b
 (B499)c
CYP24A1 [Cytochrome P450, family 24, subfamily A, polypeptide 1]c.1186C>Tp.Arg396Trphom1.00, D.r.19M5NLN/ANLHC/NLAvoidance of exogenous Vitamin D and extreme sunlight, monitor for hypercalcemia with peptic ulcers and pancreatitis, genetic counseling
c.1147G>Cp.Glu383Glncomp1.00, D.r.NovelF0.8NCCaOxIdiopathic HCHC/NL
c.428_430delp.Glu143delhetN/A, D.r.19
 (B540)b
 (B607)b
SLC12A1 [Sodium/potassium/chloride transporter] (B446)bc.2755G>Cp.Asp919Hishom1.00, G.g.NovelF0.3NCN/ABSBSTreatment with indomethacin and electrolyte substitution, genetic counseling
AGXT [Alanine-gloxylate aminotransferase] (B424)bc.508G>Ap.Gly170Arghom1.00, D.r.12F0.6NCCaOxPrimary hyperoxaluriaPH1Trial treatment with pyridoxine, ophthalmology screen, cardiac screen, monitor for oxalates and tissue calcification, genetic counseling
OCRL [Oculocerebrorenal syndrome of Lowe]c.1484C>Tp.Pro495Leuhem1.00, D.r.37M10NLN/ALSLS/DD2Consult with ophthalmology, monitor for seizures, genetic counseling
c.2510G>Ap.Arg837Hishem0.23, D.r.NovelM7NLCaOxIdiopathic HCLS/DD2
 (B422)b
 (B199)b
  • PPh2, Polyphen2-HumVar (http://genetics.bwh.harvard.edu/pph2/); NL, nephrolithiasis; NC, nephrocalcinosis; H+, proton; hom, homozygous; X.t., Xenopus tropicalis; M, male; CaOx, calcium oxalate; dRTA, distal renal tubular acidosis; ↑, increased; K+, potassium; comp het, compound heterozygous; F, female; n/a, not available; HC, hypercalciuria; HK, hypokalemia; FHHNC, familial hypomagnesemia with hypercalciuria and nephrocalcinosis; D.r., Dario rerio; HM, hypomagnesemia; HOMG5, hypomagnesemia 5, renal, with ocular involvement; HO, hyperoxaluria; N/A, not available; G.g., Gallus gallus; BS, Bartter syndrome; PH1, primary hyperoxaluria, type 1; hem, hemizygous; LS, Lowe syndrome; DD2, Dent disease 2.

  • a Practical implications are based off the defined Online Mendelian Inheritance of Man database phenotype (http://www.omim.org).

  • b Patients derive from the Balkan region.

  • c Patients are American.