RFX6 is needed for the development and maintenance of the β-cell phenotype

Departments of Pediatrics and Human Genetics, McGill University, Montreal, QC, Canada.
Islets (Impact Factor: 1.49). 09/2011; 3(5):291-3. DOI: 10.4161/isl.3.5.15944
Source: PubMed


RFX6 has recently been found to be essential for the development of the endocrine pancreas through studies in both humans and mice. Interestingly, this gene maintains a specific expression in the postnatal hormone producing cells of the pancreas. Moreover in humans, different types of diabetes mellitus affect obligate carriers of RFX6 mutations. Therefore, RFX6 appears to have a pivotal role in the maintenance of the phenotype of the β-cells in addition to their development. Extensive research is needed to specify this role and explore its significance in the efforts to treat diabetes with medications, or more importantly, through β-cell replacement.

Download full-text


Available from: Constantin Polychronakos, Dec 23, 2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Developing cell-based diabetes therapies requires examining transcriptional mechanisms underlying human β cell development. However, increased knowledge is hampered by low availability of fetal pancreatic tissue and gene targeting strategies. Rodent models have elucidated transcription factor roles during islet organogenesis and maturation, but differences between mouse and human islets have been identified. The past 5 years have seen strides toward generating human β cell lines, the examination of human transcription factor expression, and studies utilizing induced pluripotent stem cells (iPS cells) and human embryonic stem (hES) cells to generate β-like cells. Nevertheless, much remains to be resolved. We present current knowledge of developing human β cell transcription factor expression, as compared to rodents. We also discuss recent studies employing transcription factor or epigenetic modulation to generate β cells.
    No preview · Article · May 2014 · Trends in Endocrinology and Metabolism
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Identification of the genetic defect underlying early-onset diabetes is important for determining the specific diabetes subtype, which would then permit appropriate treatment and accurate assessment of recurrence risk in offspring. Given the extensive genetic and clinical heterogeneity of the disease, high-throughput sequencing might provide additional diagnostic potential when Sanger sequencing is ineffective. Our aim was to develop a targeted next-generation assay able to detect mutations in several genes involved in glucose metabolism. All 13 known MODY genes, genes identified from a genome-wide linkage study or genome-wide association studies as increasing the risk of type 2 diabetes and genes causing diabetes in animal models, were included in the custom panel. We selected a total of 102 genes by performing a targeting re-sequencing in 30 patients negative for mutations in the GCK, HNF1α, HNF4α, HNF1β and IPF1 genes at the Sanger sequencing analysis. Previously unidentified variants in the RFX6 gene were found in three patients and in two of them we also detected rare variants in WFS1 and ABCC8 genes. All patients showed a good therapeutic response to dipeptidyl peptidase-4 (DPP4) inhibitors. Our study reveals that next-generation sequencing provides a highly sensitive method for identification of variants in new causative genes of diabetes. This approach may help in understanding the molecular etiology of diabetes and in providing more personalized treatment for each genetic subtype.The Pharmacogenomics Journal advance online publication, 22 July 2014; doi:10.1038/tpj.2014.37.
    Full-text · Article · Jul 2014 · The Pharmacogenomics Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Martinez-Frias Syndrome (MFS) is a rare disorder characterized as an autosomal recessive disease. It has been described as a disorder of duodenal atresia, extrahepatic biliary atresia, hypoplastic pancreas, intrauterine growth retardation (IUGR), and initially described with tracheoesophageal fistula. We present a case report of a preterm infant with a diagnosis of MFS, and a review of the literature. The constellation of symptoms described varies between the limited number of cases reported; this case presented is rare as the patient’s course was complicated by cerebral ischemia something not previously described.
    Full-text · Article · Nov 2014 · Journal of Pediatric Surgery Case Reports
Show more