The FMR1 gene is associated with Fragile X syndrome, the most common form of intellectual disability. Researchers have now linked the gene to several other conditions includin​g bone and connective tissue disorders, depression and urinary tract issues.

Researchers at Marshfield Clinic Research Institute and University of Wisconsin-Madison recently published this research in the journal Science Advances.

The FMR1 gene is on the X-chromosome and can contain a repeat of three nucleotides (CGG) ranging from less than 20 to more than 200. Repeats greater than 200 lead to Fragile X syndrome. Repeats in the range of 55-200 are defined as “premutation", as they can expand to full mutation in subsequent generations. Research has already shown this gene increases the risk for irregular menstrual bleeding and infertility and for neurodegenerative and motor symptoms after the age of 50.

 “This study discovered new health conditions in both males and females associated with carriers of this premutation," said Murray Brilliant, Ph.D., senior research scientist for the Center for Precision Medicine Research and primary investigator for this research from the Research Institute. “This underscores the importance of future genetic testing for this FMR1 gene."

These findings confirmed a risk for irregular menstrual bleeding and infertility in premutation carriers and further discovered bone and connective tissue disorders, anxiety disorders (agoraphobia and panic disorders), mood and depressions disorders, breathing problems, urinary tract problems and much more.

Patient data and DNA samples for the research came from Marshfield Clinic Health System patients enrolled in the Personalized Medicine Research Project at the Research Institute.

“The unique contribution of Health System patients in the Personalized Medicine Research Project were key to these discoveries," said Dr. Brilliant. “We were able to look at this FMR1 gene in detail because we could do it on a large scale and in an unbiased way."

Leading the project was Arezoo Movaghar, M.S., and Marsha R. Mailick, Ph.D., from the Waisman Center at the University of Wisconsin-Madison. The group also partnered with the Department of Biomedical Engineering, Department of Biostatistics and Medical Informatics and Morgridge Institute for Research at the University of Wisconsin-Madison; Wisconsin State Laboratory of Hygiene; and the Rush University Medical Center in Chicago.

This work was supported by the NIH National Institute of Child Health and Human Development. The Personalized Medicine Research Project is supported by National Human Genome Research Institute and National Center for Advancing Translational Science. Additional support came from the Wisconsin Alumni Research Foundation; the Centers for Disease Control and Prevention; and National Center on Birth Defects and Developmental Disabilities.