Genetic Mutation Discovered in Familial Chronic Diarrhea Syndrome

One heritable DNA mutation has been discovered that leads to chronic diarrhea and bowel inflammation, which contributes the pathology of the diseases.

A protein made from a specific gene is involved in transmitting specific chemical signals from food consumed to the cells inside the bowels, but family members with chronic diarrhea have a mutation that makes the protein transmit more signal than it should.

Investigators at HudsonAlpha Institute for Biotechnology (Huntsville, AL, USA) working with scientists from Norway and India, studied a Norwegian family with a number of related inflammatory bowel conditions. There were 32 affected persons from three branches of the same family as well as 14 unaffected family members. Such a large family allowed scientists in Norway to use traditional methods to narrow down the potential DNA mutation to one portion of chromosome 12, and then to a specific gene called guanylate cyclase 2C (GUCY2C). They used linkage analysis, based on arrays with single-nucleotide polymorphisms (SNPs), to identify a candidate region.

Genomic DNA was purified from blood with the use of the QIAsymphony system (Qiagen, Germantown, MD, USA). Whole-genome genotyping of SNPs was performed with the use of GeneChip Human Mapping Array (Affymetrix, Santa Clara, CA, USA). Linkage analysis of samples from 11 affected members and 14 healthy members of one family branch revealed only one significant shared region in the affected members, on the short arm of chromosome 12. The scientists are now evaluating possible drug treatments based on the function of the affected protein. They can also recommend that GUCY2C be reexamined in more common bowel inflammation syndromes, as it may contribute to pathology for thousands of people worldwide.

Shawn E. Levy, PhD, a faculty investigator at HudsonAlpha said, "Based on the effects seen from this one mutation, we are hopeful that the work will aid in understanding of much more common diseases like Crohn's and irritable bowel syndrome, which also have inflammation and diarrhea as symptoms." The study was published on March 21, 2012, in the New England Journal of Medicine (NEJM).

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HudsonAlpha Institute
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Affymetrix