NKCC2, ROMK, and CLCNKB genes

Mutations of these genes account for the highly genetic hetero­geneous disorder represented by Bartter’s syndrome. This dis­ease consists of a set of renal tubular disorders, inherited as autosomal recessive trait, clinically characterized by chronic hypokaliemia, metabolic alkalosis, hyperreninism and hyperal- dosteronism with normal values of blood pressure: Antenatal (with hyperproduction of type E Prostaglandins) and Classical forms of Bartter’s syndrome. PH is presented on both these forms. Other additional biochemical and clinical features deter­mine a different tubulopathies phenotype classification: Antenatal form consists of type I, II and IV Bartter’s syndrome, while Classical form is also indicated as type III Bartter’s syn­drome. Mutations of the responsible genes create a se­vere disturbance in maintaining the electric driving force at tubular level regulating the paracellular transportation (from lu­men to blood) of calcium. 1 internet online drugstore

NKCC2 gene. It encodes for the Na+/K+/Cl2 co-transporter, a membrane protein expressed on the lumen side of tubular cells at TAL level, that physiologically determines the entry of the above-described ions from lumen within the cell. Its mutations have been reported in Antenatal Bartter’s syndrome preventing the entry of Na+/K+/Cl2 from the lumen side.

ROMK gene. The encoded product of this gene is a potassium channel protein whose function consists of recycling of K+, en­tered through NKCC2, from intracellular store to the tubular lu­men. It is essential for the function of NKCC2 itself. It has been found mutated in Antenatal Bartter’s syndrome. Transfection experiments of rat mutated ROMK-cDNA in COS-7 cells are able to reduce or destroy the electrophysiological properties of the channel-protein, preventing the K+ recycling.

ClCNKB gene. It encodes for the human Chloride channel (hClC-KB) and its mutations alter the transportation, at the basolateral membrane level, of the Chloride reabsorbed through hClC-KB in the distal part of nephron .