The patients were mostly male and were found to have at least one allele of a splice defect on the SLC12A3 gene. Cause
The sodium chloride symporter is a protein made up of 1021 amino acids and 12 transmembrane domains. Mutations that occur on the SLC12A3 gene range from missense, nonsense, frame-shift and splice-site mutations which occur throughout the gene.Most cases of Gitelman syndrome are linked to inactivating mutations in the SLC12A3 gene, resulting in a loss of function of the thiazide-sensitive sodium-chloride co-transporter (NCCT). This genetic mutation in SLC12A3 is present in 80% of adults with Gitelman syndrome. More than 180 mutations of this transporter protein have been described. This cell membrane protein participates in the control of ion homeostasis at the distal convoluted tubule portion of the nephron. Loss of this transporter also has the indirect effect of increasing calcium reabsorption in a transcellular fashion. This has been suggested to be the result of a putative basolateral Na+/Ca2+ exchanger and apical calcium channel.When the sodium-chloride cotransporter (NCCT) is inactivated, continued action of the basolateral Na+/K+-ATPase creates a favourable sodium gradient across the basolateral membrane. This increases the reabsorption of divalent cations by secondary active transport. It is currently unknown why calcium reabsorption is increased while magnesium absorption is decreased, often leading to a low level of magnesium in the blood .A secondary effect of the inactivated sodium-chloride cotransporter is the subsequent activation of the renin-angiotensin aldosterone system (RAAS).
Corneal ectatic disorders or corneal ectasia are a group of uncommon, noninflammatory, eye disorders characterised by bilateral thinning of the central, paracentral, or peripheral cornea. Types
Keratoconus, a progressive, noninflammatory, bilateral, asymmetric disease, characterized by paraxial stromal thinning and weakening that leads to corneal surface distortion. Keratoglobus, a rare noninflammatory corneal thinning disorder, characterised by generalised thinning and globular protrusion of the cornea. Pellucid marginal degeneration, a bilateral, noninflammatory disorder, characterized by a peripheral band of thinning of the inferior cornea. Posterior keratoconus, a rare condition, usually congenital, which causes a nonprogressive thinning of the inner surface of the cornea, while the curvature of the anterior surface remains normal. Usually only a single eye is affected. Post-LASIK ectasia, a complication of LASIK eye surgery. Terriens marginal degeneration, a painless, noninflammatory, unilateral or asymmetrically bilateral, slowly progressive thinning of the peripheral corneal stroma. Diagnosis
Usually diagnosed clinically by several clinical tests. Although some investigations might needed for confirming the diagnosis and to differentiate different types of corneal ectatic diseases. Corneal topography
Corneal tomography

Treatment
Treatment options include contact lenses and intrastromal corneal ring segments for correcting refractive errors caused by irregular corneal surface, corneal collagen cross-linking to strengthen a weak and ectatic cornea, or corneal transplant for advanced cases. References
External links
International Journal of Keratoconus and Ectatic Corneal Diseases