Publications by authors named "Dagfinn Aarskog"

5 Publications

  • Page 1 of 1

SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling.

Am J Hum Genet 2013 Jul 27;93(1):150-7. Epub 2013 Jun 27.

K.G. Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway.

The phosphatidylinositol 3 kinase (PI3K) pathway regulates fundamental cellular processes such as metabolism, proliferation, and survival. A central component in this pathway is the p85α regulatory subunit, encoded by PIK3R1. Using whole-exome sequencing, we identified a heterozygous PIK3R1 mutation (c.1945C>T [p.Arg649Trp]) in two unrelated families affected by partial lipodystrophy, low body mass index, short stature, progeroid face, and Rieger anomaly (SHORT syndrome). This mutation led to impaired interaction between p85α and IRS-1 and reduced AKT-mediated insulin signaling in fibroblasts from affected subjects and in reconstituted Pik3r1-knockout preadipocytes. Normal PI3K activity is critical for adipose differentiation and insulin signaling; the mutated PIK3R1 therefore provides a unique link among lipodystrophy, growth, and insulin signaling.
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July 2013

Effect of pramipexole on RLS symptoms and sleep: a randomized, double-blind, placebo-controlled trial.

Sleep Med 2008 Dec 25;9(8):874-81. Epub 2008 Oct 25.

Institute San Raffaele Turro, Milan, Italy.

Background: Patients with Restless Legs Syndrome (RLS) often seek treatment because of sleep problems related to nocturnal symptoms. Our goal was to test the ability of pramipexole to improve sleep in RLS patients and to reconfirm its efficacy for primary RLS symptoms.

Methods: Adults with moderate or severe RLS were randomized to receive placebo or pramipexole (flexibly titrated from 0.25 to 0.75mg), 2-3h before bedtime for 12 weeks. The co-primary outcome measures were change in Medical Outcomes Study (MOS) sleep disturbance score and International RLS Study Group Rating Scale (IRLS) score at 12 weeks.

Results: The intent-to-treat population included 357 patients: 178 received pramipexole and 179 received placebo. At 12 weeks, the adjusted mean change from baseline was greater for pramipexole (vs. placebo) for IRLS score (-13.4+/-0.7 vs. -9.6+/-0.7) and MOS sleep disturbance score (-25.3+/-1.5 vs. -16.8+/-1.5) (p
Conclusions: Pramipexole is effective and well-tolerated for RLS and related sleep disturbance.
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December 2008

Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes.

Diabetes 2008 Apr 11;57(4):1131-5. Epub 2008 Jan 11.

Gade Institute, University of Bergen, Norway.

Objective: Mutations in the insulin (INS) gene can cause neonatal diabetes. We hypothesized that mutations in INS could also cause maturity-onset diabetes of the young (MODY) and autoantibody-negative type 1 diabetes.

Research Design And Methods: We screened INS in 62 probands with MODY, 30 probands with suspected MODY, and 223 subjects from the Norwegian Childhood Diabetes Registry selected on the basis of autoantibody negativity or family history of diabetes.

Results: Among the MODY patients, we identified the INS mutation c.137G>A (R46Q) in a proband, his diabetic father, and a paternal aunt. They were diagnosed with diabetes at 20, 18, and 17 years of age, respectively, and are treated with small doses of insulin or diet only. In type 1 diabetic patients, we found the INS mutation c.163C>T (R55C) in a girl who at 10 years of age presented with ketoacidosis and insulin-dependent, GAD, and insulinoma-associated antigen-2 (IA-2) antibody-negative diabetes. Her mother had a de novo R55C mutation and was diagnosed with ketoacidosis and insulin-dependent diabetes at 13 years of age. Both had residual beta-cell function. The R46Q substitution changes an invariant arginine residue in position B22, which forms a hydrogen bond with the glutamate at A17, stabilizing the insulin molecule. The R55C substitution involves the first of the two arginine residues localized at the site of proteolytic processing between the B-chain and the C-peptide.

Conclusions: Our findings extend the phenotype of INS mutation carriers and suggest that INS screening is warranted not only in neonatal diabetes, but also in MODY and in selected cases of type 1 diabetes.
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April 2008

[Primary adrenal failure--causes, diagnostics and therapy].

Tidsskr Nor Laegeforen 2005 Jan;125(2):155-8

Institutt for indremedisin, Universitetet i Bergen, Medisinsk avdeling Haukeland Universitetssykehus.

Background And Methods: An overview of primary adrenal failure with emphasis on replacement therapy is presented. The article is based on a review of recent literature and authors' personal experience.

Results And Conclusions: Addison's disease is usually caused by an autoimmune destruction of the adrenal cortex. It is relatively rare (prevalence 14 per 100,000 inhabitants), but often considered as a differential diagnosis when evaluating fatigue, tiredness and loss of weight. Addison's disease is treated by repletion of glucocorticoids and mineralocorticoids. The recommended starting dose is 25 mg cortisone acetate per day divided into three (12.5 + 6.25 + 6.25 mg) or two doses (12,5 mg x 2). Mineralocorticoid replacement is given as fludrocortisone 0.05 - 0.2 mg in one dose per day. Treatment with 20 - 50 mg dehydroepiandrosterone has been studied in adrenal failure, but the evidence for positive effects is weak, and it can not be recommended as standard treatment in primary adrenal failure.
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January 2005