Table 1. Mendelian syndromes of hypertension and hypotension.
Shown below are the genes that are well described to harbor rare mutations that cause Mendelian forms of hypertension and hypotension. Different mutations in some of the same genes (*) can lead to both hyper- or hypo-tension depending on whether they result in gain or loss of protein function.
| gene | gene name (alias) | disease | gain(+) or loss(−) of function |
refs |
|---|---|---|---|---|
| Hypertension | ||||
| CYP11B1 | cytochrome P450, family 11, subfamily B, polypeptide 1 | 11 β hydroxylase deficiency | − | [22] |
| CYP11B2* | cytochrome P450, family 11, subfamily B, polypeptide 2 (aldosterone synthase) |
glucocorticoid remediable aldosteronism | + | [23] |
| CYP17A1 | cytochrome P450, family 17, subfamily A, polypeptide 1 | combined 17α-hydroxylase/17,20-lyase deficiency |
− | [24,25] |
| CYP17A1 | cytochrome P450, family 17, subfamily A, polypeptide 1 | isolated 17,20-lyase deficiency | − | [26] |
| HSD11B2 | hydroxysteroid (11-beta) dehydrogenase 2 | apparent mineralocorticoid excess | − | [27,28] |
| NR3C2* | mineralocorticoid receptor (MCR) | mineralocorticoid receptor mutation | + | [29] |
|
SCNN1B* SCNN1G* |
sodium channel, nonvoltage-gated 1 beta and gamma subunits |
Liddle’s Syndrome | + | [30– 32] |
| WNK1 | WNK lysine deficient protein kinase 1 | pseudohypoaldosteronism type II (Gordon Syndrome) |
+ | [33] |
| WNK4 | WNK lysine deficient protein kinase 4 | pseudohypoaldosteronism type II (Gordon Syndrome) |
−/+ | [33– 35] |
| Hypotension | ||||
| BSND | Bartter syndrome, infantile, with sensorineural deafness | Bartter’s syndrome Type 4 | − | [36] |
| CASR | calcium-sensing receptor | Bartter’s syndrome Type 5 | + | [37,38] |
| CLCNKB | chloride channel Kb | Bartter’s syndrome Type 3 | − | [39] |
| CYP11B2* | cytochrome P450, family 11, subfamily B, polypeptide 2 | corticosterone methyloxidase type I and II deficiency |
− | [40,41] |
| CYP21A2 | cytochrome P450, family 21, subfamily A, polypeptide 2 | 21-hydroxylase deficiency | − | [42,43] |
| HSD3B2 | hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 |
3 β hydroxysteroid dehydrogenase deficiency type II |
− | [44] |
| KCNJ1 | potassium inwardly-rectifying channel, subfamily J, member 1 (ROMK) |
Bartter’s syndrome Type 2 | − | [45] |
| NR3C2* | mineralocorticoid receptor | pseudohypoaldosteronism type I | − | [46] |
|
SCNN1A SCNN1B* SCNN1G* |
sodium channel, nonvoltage-gated 1 alpha, beta and gamma subunits |
pseudohypoaldosteronism type I | − | [47] |
| SLC12A1 | solute carrier family 12 member 1 (Na-K-2Cl cotransporter, NKCC2, loop diuretic target) |
Bartter’s syndrome Type 1 | − | [48] |
| SLC12A3 | solute carrier family 12 member 3 (Na-Cl cotransporter, NCCT, thiazide diuretic target) |
Gitelman’s syndrome | − | [49] |
*
gene associated with both hypertension and hypotension