+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Mosaic paternal uniparental isodisomy and an ABCC8 gene mutation in a patient with permanent neonatal diabetes and hemihypertrophy

, : Mosaic paternal uniparental isodisomy and an ABCC8 gene mutation in a patient with permanent neonatal diabetes and hemihypertrophy. Diabetes 57(1): 255-258

OBJECTIVE-Activating mutations in the KCNJ11 and ABCC8 genes encoding the Kir6.2 and SUR1 subunits of the pancreatic ATP-sensitive K+ channel are the most common cause of permanent neonatal diabetes. In contrast to KCNJ11, where only dominant heterozygous mutations have been identified, recessively acting ABCC8 mutations have recently been found in some patients with neonatal diabetes. These genes are co-located on chromosome 11p15.1, centromeric to the imprinted Beckwith-Wiedemann syndrome (BWS) locus at 11p15.5. We investigated a male with hemihypertrophy, a condition classically associated with neonatal hyperinsulinemia and hypoglycemia, who developed neonatal diabetes at age 5 weeks.RESEARCH DESIGN AND METHODS-The KCNJ11 and ABCC8 genes and microsatellite markers on chromosome 11 were analyzed in DNA samples from the patient and his parents.RESULTS-A paternally inherited activating mutation (N72S) in the ABCC8 gene was identified in the proband. The mutation was present at 70% in the patient's leukocytes and 50% in buccal cells. Microsatellite analysis demonstrated mosaic segmental paternal uniparental isodisomy (UPD) of 11pter-11p14 in the proband that encompassed the ABCC8 gene and the BWS locus.CONCLUSIONS-We report a patient with neonatal diabetes, hemihypertrophy, and relatively high birth weight resulting from telomeric segmental paternal UPD of chromosome 11, which unmasks a recessively acting gain-of-function mutation in the ABCC8 gene and causes deregulation of imprinted genes at the BWS locus on 11p15.5.


PMID: 17942821

DOI: 10.2337/db07-0999

Other references

Berrie, C.P.; Cobbold, P.H., 1995: Both activators and inhibitors of protein kinase C promote the inhibition of phenylephrine-induced [Ca2+]i oscillations in single intact rat hepatocytes. In single isolated rat hepatocytes Ca(2+)-mobilising hormones induce oscillations in cytosolic free Ca2+ ([Ca2+]i) in which the frequency of spiking depends on agonist dose, but the time course of individual spikes depends on the hormone species,...

Sopper, S.; Nierwetberg, D.; Halbach, A.; Sauer, U.; Scheller, C.; Stahl-Hennig, C.; Mätz-Rensing, K.; Schäfer, F.; Schneider, T.; ter Meulen, V.; Müller, J.G., 2002: Impact of simian immunodeficiency virus (SIV) infection on lymphocyte numbers and T-cell turnover in different organs of rhesus monkeys. HIV infection leads to reduced numbers and increased turnover of CD4+ T cells in blood. However, blood represents only 2% of the total lymphocyte pool, and information about other organs is lacking, leading to controversy about the effects of HIV...

A'arabi, S.Y.; Mailhes, J.B.; Young, D.; Roussel, J.D., 1996: Cytogenetic abnormalities of oocytes maturation in four different culture media. Journal of Animal Science 74(SUPPL 1): 217

Mourao, G.S.; Hodes, J.E.; Gobin, Y.P.; Casasco, A.; Aymard, A.; Merland, J.J., 1991: Curative treatment of scalp arteriovenous fistulas by direct puncture and embolization with absolute alcohol. Report of three cases. Three cases of direct arteriovenous fistulas of the scalp (two involving cirsoid aneurysms) are presented. All three patients were treated with direct puncture of the venous pouch and injection of absolute ethyl alcohol during compression of the v...

Khokhlova, S.M.; Irzhanskaia, K.N., 1974: Some indices of histamine metabolism in adolescents with chronic tonsillitis. Pediatriia Akusherstvo i Ginekologiia 3(0): 26-28

Finlayson, M.K.; Edson, N.L., 2012: The use of yolk-enriched egg medium for the cultivation of tubercle bacilli. New Zealand Medical Journal 46(253): 190-198

Montandon, A.L., 1913: Nepidae et Belostomatidae, descriptions de deux especes nouvelles. Bucarest Bul Soc Sci, 22 122-125

Camdessanché, J-Philippe.; Antoine, J-Christophe., 2015: Sensory neuronopathy: diagnostic strategy. Sensory neuronopathy (SNN) depends on a pathophysiological process that targets the sensory neuron in the posterior root ganglia. These rare diseases are sometimes difficult to diagnose because the site of impairment is not directly assessable by...

Grudzinski I.; Szymanski A., 1991: The effect of subchronic poisoning with potassium nitrate and sodium nitrite on the processes of intestinal absorption with d xylose in rats. The intestinal transport of D-xylose was studied during subchronic poisoning of male Wistar rats with the oral administration of potassium nitrate and sodium nitrite. The metabolic parameters of small intestine mucosa were determined one hour afte...

Gorenflot, R., 1960: Polyploidy in Plantago coronopus L. Plantago coronopus L. appears to be either a highly polymorphic and unstable species or else a group of similar and freely interbreeding species. The group as a whole i6 diploid with the chromosome number 2n = 10. Scattered over North Africa there...