The discovery of a gene that causes a rare, inherited and always fatal disorder, Meckel-Gruber (MKS) syndrome, may provide researchers with the common thread to unravel the mysteries of other birth defects.

Identification of the gene was announced in Nature Genetics by an international team of researchers from Indiana University School of Medicine, Mayo Clinic and University of Birmingham-UK.

The collaboration was co-led by Vincent Gattone, Ph.D., professor of anatomy and cell biology at Indiana University School of Medicine; Peter Harris, Ph.D., a nephrology researcher at Mayo Clinic; and Colin Johnson from the University of Birmingham - UK.

The gene that was initially identified in an animal model maintained by Dr. Gattone was further evaluated in MKS patients that shared similar types of developmental defects with the rodent model including polycystic kidney disease (PKD) and abnormal brain development.

Children with MKS have central nervous system deformities and abnormal cysts in their kidneys, along with other impairments, and typically die shortly after birth. Although rare, Merkel-Gruber syndrome is associated with a more common kidney disease, polycystic kidney disease (PKD), which is the focus of Dr. Gattone’s research. PKD is the most common inherited cause of renal failure in the United States and MKS is the most common syndrome that causes neural tube defects.

Knowing the identity of one of the key genes involved in MKS is the first step to understanding the disorder and eventually developing therapies to better treat or prevent it.

“Identifying similarities among genetic diseases in rodents and humans is key to discoveries such as the identification of the MKS3 gene,” said Dr. Gattone. “With this discovery and the availability of an animal model, researchers may now have a tool to advance their insights into how MKS develops.”

The discovery of the MKS3 gene is relevant for researchers trying to understand how cysts develop in kidneys. The genetic discovery also may help researchers better understand some congenital neural tube defects such as hydrocephalus.

The international research team was supported by grants from the National Institutes of Health, the Polycystic Kidney Disease Foundation, Mayo Clinic, the Wellcome Trust, the United Kingdom Birth Defect Foundation, University of Birmingham Medical School Scientific Programs and Birmingham Women’s Hospital Research Fund.

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