McLeod Listing of Blutspende Zurich at NCBI Genetic Testing Registry

by Christoph Gassner

McLeod Neuroacanthocytosis and Chronic Granulomatous Disease (CGD), are associated with mutations directly in the so called XK locus, located on chromosome X, or more or less large deletions of genetic material around this locus. In case of large deletions, another gene the Cytochrome b(-245) (CYBB), may also be affected and cause a lack of microbicidal superoxide, usually used to kill certain ingested pathogens.

The neurological consequences of McLeod, however, are less well understood and seem to be tightly associated with XK. The protein Kx of the gene XK on the other hand, acts as an anchor for the KELL blood group antigen in the erythrocyte membrane. And this is where blood donation services come into play, since a lack of Kx automatically leads to a pronounced or complete lack of blood group KELL antigens on the erythrocyte membranes and may be observed by chance among blood donors and patients.

Within the last two years, genetic methods to detect deletions around, or other mutations within the XK gene itself have been developed in the Department for Molecular Diagnostics & Cytometry (MOC) of Blutspende Zurich. Controversely to Duncan MacLeod “Highlander – There Can Be Only One”, “McLeod syndrome” affected males are more frequent, but only present in 0.5 to 1 per 100,000 in the population. So far, only 3 McLeod syndrome patients could be molecularly defined at Blutspende Zurich, and will be reported soon. Whereas the “Finnish” and “Turkish” patients showed large X-chromosomal deletions (red rectangles), the “Bavarian” patient had a mutated XK gene.

However, diagnostic work-up seems reliable and led to the official listing of the Blutspende Zurichs’ MOC lab in the Genetic Testing Registry (GTR) of the National Center for Biotechnology Information (NCBI).

↗ GTR: Genetic Testing Registry of the NCBI