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We have created early-onset transgenic (Tg) models by exploiting the synergistic effects of familial Alzheimer's disease mutations on amyloid beta-peptide (Abeta) biogenesis. TgCRND8 mice encode a double mutant form of amyloid precursor protein 695 (KM670/671NL+V717F) under the control of the PrP gene promoter. Thioflavine S-positive Abeta amyloid deposits(More)
Meier-Gorlin syndrome is a rare autosomal recessive genetic condition whose primary clinical hallmarks include small stature, small external ears and small or absent patellae. Using marker-assisted mapping in multiple families from a founder population and traditional coding exon sequencing of positional candidate genes, we identified three different(More)
The mouse igf2 gene, coding for the insulin-like growth factor II (IGF-II) is parentally imprinted, only the gene copy derived from the father is expressed. To know whether IGF2, the human homologue, is also imprinted, we used an ApaI polymorphism at the 3' untranslated region in order to distinguish between mRNA derived from each copy of the gene in(More)
It has been previously shown that adrenocortical tumors (ACT) in adults exhibit structural abnormalities in tumor DNA in approximately 30% of cases. These abnormalities involve chromosome 11p15 and include loss of heterozygosity, paternal isodisomy, and overexpression of the gene for insulin-like growth factor II (IGF2), correlating with DNA demethylation(More)
Primary adrenal insufficiency (PAI) in the pediatric population (0-18 yr) is most commonly attributed to congenital adrenal hyperplasia (CAH), which occurs in about 1 in 15,000 births, followed by Addison's disease, with an assumed autoimmune etiology. However, molecular advances have increased the number of possible diagnoses. The objective of this study(More)
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disease causing a wide spectrum of autoimmune dysfunction potentially including diabetes of an autoimmune etiology. We have previously described a pair of discordant APECED siblings and pointed to a possible role of 5'insulin variable number of tandem repeats (VNTR)(More)
The minisatellite DNA polymorphism consisting of a variable number of tandem repeats (VNTR) at the human INS (insulin gene) 5'-flanking region has demonstrated allelic effects on insulin gene transcription in vitro and has been associated with the level of insulin gene expression in vivo. We now show that this VNTR also has effects on the nearby(More)
Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is a major determinant of circulating levels of the IGFs and is clinically useful for the evaluation of GH deficiency and for predicting the response to GH treatment. Recent studies provide evidence that the circulating level of IGFBP-3 is inversely related to the risk of several common cancers,(More)
An 11-year-old boy with hypertension was suspected of having bilateral adrenal pheochromocytomas and hyperplasia. Molecular analysis of specific tumor suppressor genes and oncogenes excluded the familial syndromes, von Hippel-Lindau (VHL) disease and multiple endocrine neoplasia (MEN) type 2A. Further evaluation identified a unilateral adrenal(More)