See What HealthDay Can Do For You
Contact Us

Chromosome 12 Mutation Linked to Familial Diarrhea

Activating mutation in GUCY2C causes syndrome affecting 32 members of a Norwegian family

WEDNESDAY, March 21 (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, according to a study published online March 21 in the New England Journal of Medicine.

Torunn Fiskerstrand, M.D., Ph.D., 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.

Abstract
Full Text (subscription or payment may be required)

Physician's Briefing

HealthDay

HealthDay is the world’s largest syndicator of health news and content, and providers of custom health/medical content.

Consumer Health News

A health news feed, reviewing the latest and most topical health stories.

Professional News

A news feed for Health Care Professionals (HCPs), reviewing latest medical research and approvals.