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 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
ADYC10 [Adenylate cyclase 10 (soluble)]c.1052C>Ap.Pro351Hishet1.00, G.gNovelM15NLCaOxHCAbsorptive HCGenetic counseling
c.758G>Ap.Cys253Tyrhet0.69, M.m.NovelM1.5NL+NCN/AHCAbsorptive HC
 (B580)b
 (B599)b
SLC4A1 [Anion exchanger (Diego blood group)] (B280)bc.1766G>Ap.Arg589Hishet0.95, X.t.25F11NCN/AdRTA + cystsPrimary dRTAMonitor for hereditary spherocytosis, osteomalacia, hypokalemia, and periodic paralysis, genetic counseling
SLC9A3R1 [NHE3, cation proton antiporter 3] (B529)cc.328C>Gp.Leu110Valhet0.10, M.m.27F11NLN/AHPhNPHLOP2Monitor bone density, genetic counseling
SLC34A1 [Type 2 sodium/phosphate cotransporter]c.458G>Tp.Gly153Valhet1.00, D.r.NovelM4NLN/AHPh, idiopathic HCNPHLOP1/FSScreen for deafness, genetic counseling
c.398C>Tp.Ala133Valhet0.99, D.r.30M3NLN/AHPh, HCNPHLOP1/FS
c.437C>Tp.Pro146Leuhet0.95, D.r.NovelM3NLN/AHPhNPHLOP1/FS
c.1367T>Ap.Ile456Asnhet0.99, D.r.NovelF9NLCaOx, CaPhHSP, HCNPHLOP1/FS
c.1348G>Ap.Gly450Serhet0.99, D.r.NovelM7NLCaOxHPh, idiopathic HCNPHLOP1/FS
 (B491)c
 (B523)c
 (B484)c
 (B610)b,d
 (B417)c
VDR [Vitamin D (1, 25-dihydroxyvitamin D3) receptor]c.260A>Gp.Asn87Serhet0.99, D.r.NovelM12NLN/AHPhVDDR2ACalcium supplements, genetic counseling
c.1207G>Ap.Glu403Lyshet0.90, D.r.NovelF4NLN/AHPhVDDR2A
 (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.

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

  • b Patients are American.

  • c Patients derive from the Balkan region.

  • d B610 is an adopted individual and biologic family information is unavailable.