"This gene, known as Lmx1b, regulates production of other proteins that are required for normal kidney function," said Jeffrey H. Miner, Ph.D., assistant professor of medicine and of cell biology and physiology and lead author of the paper. "Our findings should improve the understanding of nail-patella syndrome and of kidney function and failure."

The findings appeared in the April 15 issue of The Journal of Clinical Investigation.

Using mice, the study found that mutations in the Lmx1b gene cause a reduction in levels of two proteins known as CD2AP and podocin. Both proteins are necessary for kidney cells known as podocytes to mature and function properly.

Podocytes form the filtering mechanism within the kidneys. Mature podocytes have long branching strands that entwine capillaries within the kidneys. Normally, these strands work with strands from neighboring cells to form a molecular meshwork, or slit diaphragms, that probably work like sieves or strainers.

"Slit diaphragms allow water and dissolved toxins like urea to leave the bloodstream while holding back protein molecules the body needs in the blood," Miner said. Much of the water is reabsorbed by the kidney and the rest, along with the urea, is collected and expelled as urine.

The study showed that podocytes from mice with the Lmx1b mutation have the appearance of immature podocytes and lack the ultrafine filter. "This helps explain why people with Lmx1b mutations and nail-patella syndrome can have kidney problems," Miner said.

Exactly how mutations in Lxm1b cause nail-patella syndrome remains poorly understood. The syndrome, which has an incidence of 4.5 cases per million people, typically causes somewhat misshaped elbows, under-formed kneecaps (patella), and pitted, wrinkled or misshaped fingernails. These abnormalities occur to different degrees in people with the syndrome.