The KCNJ1 gene encoding an important renal potassium channel causes, when mutated, autosomal recessive antenatal Bartter syndrome type 2.
Although exact data are not available, mutation in this gene are thought to occur 1 in 50,000-100,000 newborn.
The gene is expressed in epithelial cells of the thick ascending limb of the loop of Henle. The mature protein, a potassium channel, resides in the apical membrane.
As the potassium channel (ROMK) and the sodium-potassium-chloride cotransporter (NKCC2) form a functional unit, dysfuntion of either component causes the same clinical picture of autosomal recessive antenatal Bartter syndrome.
This inwardly rectifying potassium channel forms a functional unit with the sodium-potassium-chloride cotransporter. The cotransporter moves sodium and potassium, one of each ion, and two chloride from lumen into cell. The excess of sodium and chroride is removed basolateral transpoters, the sodium-potassium ATPase and a chloride channel. The excess potassium however is recycled back into the lumen by an inwardly rectifying potassium channel. Hence this channel keeps the system of net sodium chlorid reabsorption running.
WNK1 and WNK2, the genes involved in pseudohypoaldosteronism type 2, interact with intersectin-1 (ITSN1), an endocytic scaffold protein, thereby stimulating the potassium channel (ROMK) endocytosis. Hence, These genes play an important role in regulating channel function.[Error: Macro 'ref' doesn't exist]
Clinic | Method | Carrier testing |
Turnaround | 5 days | |
Specimen type | genomic DNA |
Clinic | Method | Massive parallel sequencing |
Turnaround | 25 days | |
Specimen type | genomic DNA |
Clinic | Method | Genomic sequencing of the entire coding region |
Turnaround | 10 days | |
Specimen type | genomic DNA |
Clinic | Method | Multiplex Ligation-Dependent Probe Amplification |
Turnaround | 20 days | |
Specimen type | genomic DNA |
2. |
Simon DB et al. (1996) Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK. |
3. |
He G et al. (2007) Intersectin links WNK kinases to endocytosis of ROMK1. |
4. |
Schwalbe RA et al. (1998) Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment. |
5. |
NCBI article NCBI 3758 |
6. |
OMIM.ORG article Omim 600359 |
7. |
Orphanet article Orphanet ID 122783 |
8. |
Wikipedia article Wikipedia EN (ROMK) |