(HealthDay News) – An activating mutation in GUCY2C, encoding guanylate cyclase C (GC-C), is thought to cause a novel familial diarrhea syndrome seen in a Norwegian family.

Torunn Fiskerstrand, MD, PhD, of the Haukeland University Hospital in Bergen, Norway, and colleagues describe the cause of a novel dominant disease in 32 members of a Norwegian family. Linkage analysis was used to identify a candidate region on chromosome 12, and GUCY2C was sequenced. Exome sequencing of the entire region was performed for three affected family members. Functional studies of mutant GC-C were carried out using HEK293T cells.

The researchers found that all affected family members had a heterozygous missense mutation in GUCY2C. In the candidate region, there were no other rare variants seen in exons of genes. There was a markedly increased production of cyclic guanosine monophosphate (cGMP) on exposure of the mutant receptor to its ligands.

“Increased GC-C signaling disturbs normal bowel function and appears to have a proinflammatory effect, either through increased chloride secretion or additional effects of elevated cellular cGMP,” the authors write. “Further investigation of the relevance of genetic variants affecting the GC-C-cystic fibrosis transmembrane regulator pathway to conditions such as Crohn’s disease is warranted.”

Several authors disclosed financial ties to the pharmaceutical and biotechnology industries.

Full Text (subscription or payment may be required)