A rare mutation offers wide possibilities

As they flow through veins and arteries, most red blood cells are plump with water. Channels lining the membrane of each red blood cell help ensure that it has the right balance of salts and liquids, keeping the cells elastic and healthy. It's a process vital to human biology, but also one that's been hard for researchers to fully explain.

A team including scientists at the Yale School of Medicine has now uncovered a protein that is key to how blood cells maintain their hydration, and which could have implications for treating sickle cell anemia, the most common inherited blood disorder in the United States.

The discovery came out of a quest to understand a much rarer inherited blood disorder called xerocytosis. In this disease, the equilibrium of red blood cells is off: extra potassium and water seep out of cells as they careen against the sides of blood vessels, leaving the cells fragile and causing anaemia, a shortage of red blood cells.

Sickle-cell anaemia, characterised by misshapen red blood cells, and a common complication, apart from the clumping of the misshapen cells, is cell dehydration. ''Some of the mechanisms that cause the dehydration are known, but we've never uncovered what is that channel at the top of the mountain that starts the avalanche going,'' says Patrick G. Gallagher, MD, professor of paediatrics, genetics, and pathology.

Gallagher and a team of collaborators thought that if they could understand dehydration in hereditary xerocytosis, it might help explain the similar phenomenon they see in sickle cell patients.

So, in a study supported by the Doris Duke Foundation and conducted in collaboration with a team from the University of Manitoba, they analysed the genomes of two large, multi-generational families affected by xerocytosis. In both families they identified mutations in the gene for a protein called PIEZO1.