July 27,
2006
Mutant Gene Causes Congenital Malabsorptive
Diarrhea
A newly discovered disorder
characterized by malabsorptive diarrhea and a lack of
intestinal enteroendocrine cells is caused by
mutations in Neurogenin-3 (NEUROG3), reports last week's New England Journal of Medicine.
NEUROG3 is expressed in endocrine
progenitor cells and is required for endocrine-cell development in the pancreas
and intestine. The NEUROG3 gene is therefore a candidate for the cause of a
newly discovered autosomal recessive disorder which
is characterized by generalized malabsorption and a
paucity of enteroendocrine cells. Researchers from
The investigators found that
patients had few intestinal enteroendocrine cells
positive for chromogranin A. However, the patients
had normal numbers of Paneth's, goblet, and
absorptive cells. The team identified two homozygous mutations in NEUROG3. Both
of these mutations rendered the NEUROG3 protein unable to activate NEUROD1, a
downstream target of NEUROG3. The investigators noted that the mutations
compromised the ability of NEUROG3 to bind to an E-box element in the NEUROD1
promoter. – Newsfeed from GastroHep.com
New England Journal of Medicine; 2006: 355(3): 270-80