Abstract
We analyzed the SLC4A1 gene in three Mexican patients with Hereditary Spherocytosis (HS). The promoter and all 20 exons were investigated through heteroduplex analysis and DNA sequencing. No DNA changes were detected in one of the three patients. Two well-known polymorphisms, Memphis I and the Diego-a blood group, were detected in another one. In the third, the HS phenotype could be explained by the novel 1885_1888dupCCGG mutation found in heterozygosis. This frameshift mutation is predicted to result in a truncated and unstable protein lacking normal functions.
Highlights
Hereditary spherocytosis (HS) is a variably severe form of hemolytic anemia, caused by defects in the components of red cell membranes. It is characterized by the presence of spherical, dense and osmotically fragile red cells, which are selectively trapped in the spleen (Gallagher, 2005)
The eAE1 isoform is a glycoprotein of 911 amino acids with three domains: (1) the N-terminal cytoplasmic domain, containing the binding sites for hemoglobin and some cytosolic enzymes, which acts as a membrane anchorage site for the red cell skeleton through its interactions with ankyrin, and 4.1 and 4.2 proteins; (2) the transmembrane domain, which has 14 segments spanning the lipid bilayer and is responsible for Cl–/HCO3– exchange; and (3) a short cytoplasmic C-terminal domain, containing binding sites for carbonic anhydrase II
Isoform lacks the first 65 amino acids of the N-terminal domain, since it is transcribed from a second promoter located in intron 3 of the SLC4A1 gene (Alper, 2006; Delaunay, 2002)
Summary
Hereditary spherocytosis (HS) is a variably severe form of hemolytic anemia, caused by defects in the components of red cell membranes. In a few studies of HS in Mexico, the main defective proteins observed were spectrins and AE1 (Sánchez-López et al, 2003). Several mutations of SLC4A1 have been described that result in distal renal tubular acidosis (Bruce et al, 1997; Jarolim et al, 1998; Yenchitsomanus et al, 2003, 2005).
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