Table 1.
Clinical characteristics and molecular findings in 18 survivors of IIH
| Proband no. | Sex | Age at diagnosis | GFR at first presentation of IIH (eGFR; mL/min/ 1.73 m2) | Gene | Molecular result (variant 1)/(variant 2)a |
Zygosity status | Age at last observation (years) | Renal function at last observation (eGFR; mL/min/1.73 m2) | Serum calcium (mmol/L) | 25 (OH)D3 (ng/mL) | 1,25(OH)2D3 (pg/mL) | PTH (pg/mL) | Calcium:creatinine (mg/mg) | Comment | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Nucleotide level | Amino acid level | ||||||||||||||
| 1 | f | 8/12 | 46 | CYP24A1 | (1186C>T)/ (1186C>T) | (R396W)/(R396W) | Hom | 34 | 58 | 2.49 | 25.2 | 56.7 | 22.4 | 0.04 | Nephrocalcinosis |
| 2 | f | 4/12 | 78 | SLC34A1 | (1425_1426del)/(?) | (C476Sfs*128)/(?) | Het | 28 | 70 | 2.41 | 28.2 | 36.4 | 21.7 | 0.12 | Nephrocalcinosis/Nephrolithiasis |
| 3 | f | 5/12 | 29 | CYP24A1 | (428_430del)/ (1186C>T) | (E143del)/(R396W) | Comp het | 30 | 98 | 2.49 | 36.4 | 93.6 | 20.4 | 0.14 | Nephrocalcinosis |
| 4 | m | 11/12 | 40 | CYP24A1 | (1186C>T)/(1226T>C) | (R396W)/(L409S) | Comp het | 25 | 78 | 2.4 | 21.8 | 63.2 | 8.7 | 0.19 | Nephrocalcinosis |
| 5 | m | 6/12 | 49 | SLC34A1 | (272_292del)/(464T>C) | (V91_A97del)/ (L155P) | Comp het | 28 | 84 | 2.4 | 31.5 | 42.3 | 12.6 | 0.25 | Nephrocalcinosis |
| 6 | m | 5/12 | 57 | CYP24A1 | (107delC)/(443T>C) | (P36Lfs*11)/(L148P) | Comp het | 27 | 85 | 2.5 | 32.1 | 51.8 | 7.9 | 0.16 | Nephrocalcinosis |
| 7 | f | 5/12 | 33 | CYP24A1 | (1186C>T)/ (1157 + 1G>A) | (R396W)/(?) | Comp het | 23 | 54 | 2.8 | 47.6 | 54.8 | 2.8 | 0.14 | Nephrocalcinosis |
| 8 | f | 10/12 | 40 | CYP24A1 | (1186C>T)/ (1186C>T) | (R396W)/(R396W) | Hom | 23 | 110 | 2.3 | 23.7 | 37.8 | 2.86 | 0.13 | Nephrocalcinosis |
| 9 | f | 8/12 | 49 | CYP24A1 | (428_430del)/ (1157 + 1G>A) | (E143del)/(?) | Comp het | 17 | 69 | 2.7 | 35.8 | 35.8 | 5.2 | 0.08 | Nephrocalcinosis |
| 10 | m | 8/12 | 100 | CYP24A1 | (1186C>T)/(?) | (R396W)/(?) | Het | 10 | 105 | 2.36 | 32.3 | 57.5 | 23.4 | 0.03 | Normal ultrasonography |
| 11 | m | 5/12 | 45 | CYP24A1 | (1186C>T)/(1186C>T) | (R396W)/(R396W) | Hom | 21 | 82 | 2.5 | 22.5 | 33.5 | 5.23 | 0.1 | Nephrocalcinosis |
| 12 | m | 14/12 | 24 | CYP24A1 | (964G>A)/(1186C>T) | (E322K)/(R396W) | Comp het | 30 | 50 (Rtx) | 2.49 | 34 | 119.1 | 18.2 | 0.13 | Increased echogenicity of renal pyramids since initial presentation. Disturbed cortico-medullary differentiation with increased echogenicity since puberty. ESRD at 27 years. Nephrocalcinosis. Renal transplantation |
| 13 | f | 6/12 | 56 | CYP24A1 | (475C>T)/(1226T>C) | (R159W)/(L409S) | Comp het | 32 | 77 | 2.54 | 39.5 | 74.2 | 2.86 | 0.12 | Nephrocalcinosis |
| 14 | m | 3/12 | 44 | CYP24A1 | (667A>T)/(1186C>T) | (R223*)/(R396W) | Comp het | 17 | 55 | 2.7 | 36.9 | 74.4 | 2.8 | 0.07 | Hyperchogenic pyramids at initial diagnosis. Normal renal ultrasonography at age of 17. |
| 15 | m | 3/12 | 23 | CYP24A1 | (443T>C)/(1186C>T) | (L148P)/(R396W) | Comp het | 34 | 75 | 2.54 | 27.1 | 65.1 | 2.22 | 0.1 | Nephrocalcinosis |
| 16 | f | 2/12 | 39 | SLC34A1 | (437C>T); (?) | (P146L)/(?) | Het | 2 | 90 | 2.55 | 30.5 | 83.2 | 8.15 | 0.15 | Nephrocalcinosis |
| 17 | m | 3/12 | 26 | CYP24A1 | (1186C>T)/(1226T>C) | (R396W)/(L409S) | Comp het | 38 | 55 (Rtx) | 2.59 | 37 | 67.2 | 39 | 0.08 | Increased echogenicity of renal pyramids since initial presentation. Disturbed cortico-medullary differentiation with increased echogenicity since puberty. ESRD at 34 years. Renal transplantation. |
| 18 | m | 6/12 | 46 | CYP24A1 | (443T>C)/(1186C>T) | (L148P)/(R396W) | Comp het | 26 | 80 | 2.55 | 37.6 | 73.3 | 2.49 | 0.07 | Nephrocalcinosis |
a
Variant numbering was based on the GenBank cDNA reference sequence of human CYP24A1 (NM_000782.4; NP_000773.2) and SLC34A1 (NM_003052.4; NP_003043.3), according to the guidelines of Human Genome Variation Society (HGVS; www.hgvs.org/mutnomen); single-letter abbreviations of amino acids have been used to describe molecular results at the amino acid level.
f, female; m, male; comp het, compound heterozygote; het, heterozygote, other pathogenic molecular variants not identified; hom, homozygote; Rtx, renal transplantation.