Yale researchers have identified a connection between a single gene mutation and the numerous symptoms of Lowe syndrome, a rare recessive genetic disorder.

The study, published in Developmental Cell this month, identifies the exact molecular process that produces the disease, taking scientists one step closer to developing ways to treat Lowe syndrome. Led by Pietro De Camilli, a professor at the School of Medicine, the research could also have implications for treating other diseases such as cancer and diabetes.

Lowe syndrome is a rare genetic condition that can cause cataracts, mental retardation, bone and muscle disorders in infants, and a fatal kidney dysfunction in which vital proteins are released in urine instead of being reabsorbed by the kidney. Because the recessive gene mutation is located on the X-chromosome, the disease affects only boys. According to the National Institutes of Health, Lowe syndrome affects less than 200,000 people in the U.S.

The syndrome is caused by mutations in a gene that encodes an enzyme known as OCRL. Although the gene was discovered in the mid-1990s, De Camilli said that until now, scientists were unsure of how gene mutations that affect the enzyme’s function could contribute to the multiple symptoms of Lowe syndrome.

“We didn’t know how you went from the mutant gene to the symptoms,” he said. “Nothing really held up well. Now we have come to understand the precise molecular mechanism of the disease.”

For a little over three years, De Camilli’s lab has been observing the biological processes at the molecular level in both human and monkey cells, researcher Yuxin Mao said.

In individuals who suffer from Lowe syndrome, genetic mutation destroys the normal function of OCRL, affecting kidney cells’ ability to reabsorb materials, Mao said. Proteins that should not be flushed out of the body end up released in urine.

De Camilli said these findings can also be applied to the brain. The lab work indicates that the severe mental handicaps seen in patients with Lowe syndrome may be caused when the mutated OCRL gene impairs intracellular traffic and signaling in the brain.

“There’s a remarkable degree of similarity in the brain,” De Camilli said. “We have focused primarily on the kidney, but we think that it might also be applied to the brain.”

The scientists said they hope the study will help develop ways to treat the disease, but admit that there is still a long way to go before treatment is feasible.

De Camilli said that in order to find a treatment, he must first understand the entire molecular mechanism that produces the disease in order to fix the whole sequence of steps that are going wrong, not just one particular step. He says this research lets them understand part of the sequence but not yet the whole mechanism at work.

“What we want to do is in a more solid way further prove that our finding can be directly related to the disease,” De Camilli said. “We also want to understand in more detail in what way what we’ve found in the kidney also relates to the brain.”

Heather McCrea MED ’09, who worked on the study in De Camilli’s lab, said the findings are especially relevant because they have clinical applications. The implications of the science could potentially help find answers for different, more common diseases, including cancer and diabetes, she said.

“This certainly has relevant clinical aspects,” McCrea said. “It’s really important and not just for Lowe syndrome patients.”

De Camilli said his lab will continue to work on Lowe syndrome in order to solidify the connection between the findings in this study and the other symptoms of the disease, specifically mental retardation. The final step will be to use the research to find a viable treatment for the genetic disorder, he said.