This report describes a newly identified nonsense mutation in human NEUROG3 that in the homozygous state is associated with neonatal diabetes and malabsorptive diarrhea.
Recent studies have established that the T1R3 receptor plays a central role in the taste-mediated ingestive response to sweeteners by mice. First, transgenic mice lacking the gene for T1R3, Tas1r3, show dramatically reduced lick responsiveness to most sweeteners. Second, strains with the taster allele of Tas1r3 (T strains) are more sensitive to low sweetener concentrations than strains with the nontaster allele (NT strains) and consume greater quantities of low- to midrange concentrations of sweeteners during 24-h tests. We asked how Tas1r3 polymorphisms influence the initial licking responses of four T strains (FVB/NJ, SWR/J, SM/J, and C57BL/6J) and four NT strains (BALB/cJ, 129P3/J, DBA/2J, and C3H/HeJ) to two sweeteners (sucrose and SC-45647, an artificial sweetener). We used the initial licking response as a measure of the taste-mediated ingestive response because its brief duration minimizes the potential contribution of nontaste factors (e.g., negative and positive postingestive feedback). Further, we used two complimentary short-term intake tests (the brief-access taste test and a novel 1-min preference test) to reduce the possibility that our findings were an epiphenomenon of a specific testing procedure. In both tests, the T strains were more responsive than the NT strains to low concentrations of each sweetener. At higher concentrations, however, there was considerable overlap between the T and NT strains. In fact, the initial licking response of several NT strains was more vigorous than (or equivalent to) that of several T strains. There was also considerable variation among strains with the same Tas1r3 allele. We conclude that Tas1r3 polymorphisms contribute to strain differences in initial lick responsiveness to low but not high concentrations of sweeteners.
Context
Heterozygous mutations in GATA6 have been linked to pancreatic agenesis and cardiac malformations.
Objective
To describe a new mutation in GATA6 in an infant with pancreatic agenesis, associated with truncus arteriosus and absent gallbladder.
Research Design and Methods
Clinical data were obtained from chart review. Gene sequencing was performed on genomic DNA.
Results
Our patient was a female diagnosed shortly after birth with a severe cardiac malformation, absent gallbladder, anomalous hepatic blood flow, unilateral hydronephrosis and hydroureter, neonatal diabetes and pancreatic exocrine insufficiency. Despite prolonged intensive management care, she expired at 2 months of age due to cardiac complications. Analysis of her genomic DNA reveled a novel missense mutation of GATA6.
Conclusions
The novel mutation described in this case extends the list of GATA6 mutations causing pancreatic agenesis and cardiac malformations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.