Gene Defect Causes Kidney Disorder

Recent findings have revealed that a mutation of the Lmx1b gene, which regulates synthesis of proteins required for normal kidney function, prevents the kidneys from filtering properly. This condition is characteristic of a rare disorder known as nail-patella syndrome. This finding was reported in the April 15, 2002, issue of The Journal of Clinical Investigation.

Podocytes are specialized cells that form the kidney's filtering mechanism. 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,” explained Dr. Jeffrey H. Miner of the Washington University School of Medicine (St. Louis MO, USA) and lead author of the paper. "Much of the water is reabsorbed by the kidney and the rest, along with the urea, is collected and expelled as urine.”

In the current study, mice with mutations in the Lmx1b gene had reduced levels of two proteins, CD2AP and podocin, which are required by podocytes to mature and function properly. Podocytes from the mutated mice appeared to be immature and lacked the molecular filter network. About 30% of people with nail-patella syndrome also have kidney problems, which can range from small amounts of blood or protein in the urine to progressive kidney failure. Why mutations in Lxm1b cause nail-patella syndrome is not yet understood.