Blood group antigens reveal their maker

摘要

For the first time, heterozygous mutations within human EKLF/KLF1 have been identified and shown to alter the expression of blood group antigens.Subtle variations in certain groups of genes may not lead to a dramatic clinical presentation, but when enriched within human subpopulations, they can serve to distinguish that group of individuals from others. Such isthe case for cell surface antigens in red blood cells. For example, the Lutheran (Lu) antigen, which consists of 2 alternatively spliced components (Lutheran and B-CAM) derived from the same gene, is widely expressed in many celltypes, but particular geographic regions (eg, southeastern England) contain a higher prevalence of individuals who do not express this blood group antigen. This group is phenotypi-callycategorized as In(Lu)(j玥ibitorofthe Lutheran antigen). Two intriguing properties noted early on were that the deficiency was tissue specific, as it occurred only in the red blood cells of such individuals, and that it behaved genetically as an independently segregating and dominant regulator unlikely to be a repressor. These observations led to a prediction that In(Lu) encodes a red cell-restricted DNA-binding protein that directly or indirectly affects the expression of the Lu antigen.1 In this issue of Blood, Singleton and colleagues now show this prediction to have been on the mark, as they demonstrate that transcription factor EKLF (KLF1) is the InLu gene.