Gitelman syndrome (GS) is a heritable disorder caused by a m…
Questions
Gitelmаn syndrоme (GS) is а heritаble disоrder caused by a mutatiоn in the SLC gene that encodes a Na+/Cl- cotransporter protein (A in Figure 1) that is expressed in kidney cells. When molecules or ions are moved by cotransporters, the molecules or ions must move across a membrane together, either in the same direction or in opposite directions. The Na+/Cl- cotransporter simultaneously transports Na+ and Cl- from one region of the kidney (Region I) into the cell. Other transporters in kidney cell membranes include the Na+/K+ ATPase (B in Figure 1) and a Na+/Ca2+ cotransporter D in Figure 1) that allow ions to move across the membrane between the kidney cell and a second region of the kidney (Region II ). Kidney cells also have channel proteins like the Ca2+ channel (C in Figure 1) that transports Ca2+ from Region I into the kidney cell. A model representing the exchange of various ions between the kidney cell and the two extracellular regions is shown in Figure 1. The size of an ion's symbol indicates the relative concentration of that ion in a given area. The larger symbol indicates the area of higher concentration, and the smaller symbol indicates the area of lower concentration. Figure 1. Model representing the exchange of ions between a kidney cell and two isolated extracellular regions. The larger symbols indicate the areas of higher ion concentration, and the smaller symbols indicate the areas of lower ion concentration. Researchers have determined that there are a number of mutations to the SLC wild-type allele (SLC) that result in GS. One mutant allele, SLC-gs1, results from a single nucleotide deletion that creates a stop codon midway through the coding region of the gene. A second mutant allele, SLC-gs2, results from a mutation that disrupts the sequence of a splicing site between an intron and an exon, preventing the removal of an intron. To better understand how GS is inherited, researchers studied a number of families with a history of GS . The pedigree of one of these families is shown in Figure 2. Figure 2. Pedigree of a family with a history of GS caused by two different mutant alleles
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