The findings appear in the current edition of Nature Genetics. In addition to Mayo Clinic, the collaboration involved researchers from the Indiana University School of Medicine in Indianapolis, and the University of Birmingham, England. Significance of the Finding

This news is of immediate importance to MKS families who may now have their blood screened for the defect and seek genetic counseling. The finding also is important for advancing understanding of what goes wrong in common birth defects, such as neural tube defects, as well as for related disorders such as more common forms of polycystic kidney disease (PKD). PKD accounts for more than 5 percent of end-stage kidney disease in the United States and Europe.

"This gene has immediate relevance for a small number of families, but the broader implications are important for the understanding they bring of how cysts develop in the kidney," explains Peter Harris, Ph.D., the Mayo Clinic nephrology researcher who led the research team. "There is a kind of common linkage among these diseases. Our hope is that this new finding will aid us to devise new treatments for a broad category of disabling disease."

Meckel-Gruber kidney disease is separate from, though related to, PKD in that some of the same things go wrong to cause the abnormal formation of cysts that disrupt kidney function. Knowing the identity of one key gene involved in MKS is a first step to understanding the disorder and eventually devising therapies to blunt its effects. Treatments are being developed for the more common forms of polycystic kidney disease.

The current work is an extension of Mayo researchers' groundbreaking work for more than a decade that has helped to reveal the genetic basis of PKD and to develop therapies. In that time, Mayo researchers have identified key genes driving the most common form of the disease in adults and in infants.

The research collaboration brought together Mayo's expertise in polycystic disease genetics with an animal model characterized in Indiana: a rat that mimicked PKD but that also showed symptoms of abnormal brain development. These clinical characteristics linked to a gene made this a useful model for an atypical form of PKD. The researchers identified the neighborhood in the model's genome where the error likely occurred, ultimately finding one gene that was defective. They then looked at the same neighborhood in the human genome for evidence of a disease with symptoms similar to the model (the bottom of chromosome 8) and found Meckel-Gruber syndrome type 3 (MKS3). Screening the corresponding gene, they identified similar changes in the MKS3 patients (characterized by the Birmingham group) and identified the disease gene.

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