MedGen

Overhydrated hereditary stomatocytosis is a variably compensated macrocytic hemolytic anemia of fluctuating severity, characterized by circulating erythrocytes with slit-like lucencies (stomata) evident on peripheral blood smears. OHST red cells exhibit cation leak, resulting in elevated cell Na+ content with reduced K+ content, with increased ouabain-resistant cation leak fluxes in the presence of presumably compensatory increases in ouabain-sensitive Na(+)-K(+) ATPase activity, and red cell age-dependent loss of stomatin/EBP7.2 (EBP72; 133090) from the erythroid membrane. Clinically, patients with OHST exhibit overhydrated erythrocytes and a temperature-dependent red cell cation leak. The temperature dependence of the leak is 'monotonic' and has a steep slope, reflecting the very large leak at 37 degrees centigrade (summary by Bruce, 2009 and Stewart et al., 2011). For a discussion of clinical and genetic heterogeneity of the hereditary stomatocytoses, see 194380. [from OMIM]

The RH-null phenotype designates rare individuals whose red blood cells lack all Rh antigens. Two RH-null types, the regulator type (RHNR) and the amorph type (RHNA; 617970), arising from independent genetic mechanisms have been distinguished. The regulator type is caused by mutation in the RHAG gene (180297), which encodes the Rh50 glycoprotein that is crucial for the surface disposition of Rh antigens. The amorph type arises from mutations at the RH locus itself that silence Rh expression. The RH locus contains the RHD (111680) and RHCE (111700) genes tandemly arranged at chromosome 1p36-p34. Four genes must therefore be silenced to produce the RH-null phenotype. The absence of the D antigen, produced by the RHD gene, is common in the human population; the D-negative phenotype may result from deletion or genetic alteration of the RHD gene. The absence of D antigen defines the Rh-negative status of the human erythrocyte (summary by Huang et al., 2000). Whereas Rh-null cells lack all Rh antigens, Rh-mod cells display a markedly reduced antigen expression. Clinically, Rh-deficient individuals exhibit a mild to moderate chronic hemolytic anemia accompanied by a varying degree of spherostomatocytosis (summary by Huang et al., 1999). [from OMIM]