Three inherited diseases have been associated with mutations in Kir channels to date, two of which are found in man and one in mouse. Bartter's syndrome is a renal tubular disorder characterised by salt-wasting, hypokalaemia and metabolic acidosis. Some Bartter's kindreds have mutations in the gene for Kir1.1. The weaver mouse results from a mutation in the pore region of Kir3.2 which makes the channel permeable to Na+ ions. The mutation leads to the selective death of brain neurones and thus to the ataxic gait that characterises the weaver phenotype. Familial persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is associated with mutations in the SUR1 or Kir6.2 subunits of the /-cell KATP channel. These result in the lack of functional KATP channel activity and lead to unregulated insulin secretion and, as a consequence, very low blood glucose levels.
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