open access

Vol 6, No 3 (2005): Practical Diabetology
Original articles (submitted)
Published online: 2005-05-16
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Mutation screening in Kir6.2 gene in subjects with permanent neonatal diabetes. Clinical characteristics and the modification of treatment method

Tomasz Klupa, Maciej T. Małecki, Joanna Nazim, Marta Ciechanowska, Jerzy Starzyk, Mieczysław Szalecki, Jacek Sieradzki
Diabetologia Praktyczna 2005;6(3):115-120.

open access

Vol 6, No 3 (2005): Practical Diabetology
Original articles (submitted)
Published online: 2005-05-16

Abstract

INTRODUCTION. Activating mutations in the KCJN11 gene encoding Kir6.2, the ATP-sensitive potassiumchannel subunit have been recently described in patients with permanent neonatal diabetes (PND).
MATERIAL AND METHODS. We examined the contribution of KCJN11 mutations to PND in patients from Poland. We sequenced the KCJN11 gene in 7 insulin treated, diabetic patients diagnosed before 6 months (range 1–26 weeks).
RESULTS. We identified three patients with de novo heterozygous missense mutations. Two males, (Pol1 and Pol2) carried the previously described R201H mutation and one female (Pol3) diagnosed at 26 weeks was a carrier of novel mutation R50Q. All three subjects with Kir6.2 mutations presented with severe hyperglycemia at the diagnosis (30–50 mmol/l). There was evidence of clinical heterogeneity: the age of diagnosis was 2, 3 and 26 weeks in Pol1, Pol2, Pol3 respectively; all were born at term with birth weights of 2450, 2700 & 3000 g and insulin requirements varied 0.25, 0.68, 0.1 U/kg. All three patients were successfully transferred to sulphonylurea therapy: Pol1 and Pol2 to sustained-release Glipizide 5 and 30 mg daily, respectively, Pol3 to 0.5 mg glimepiride.
CONCLUSION. We conclude that Kir6.2 mutations are a common cause of PND in European Caucasians and provided the evidence of clinical heterogeneity between mutation carriers. The clinical results are consistent with the novel mutation R50Q being less severe than R201H although variation between patients with R201H suggest there may be other genetic or environmental moderators of phenotype.

Abstract

INTRODUCTION. Activating mutations in the KCJN11 gene encoding Kir6.2, the ATP-sensitive potassiumchannel subunit have been recently described in patients with permanent neonatal diabetes (PND).
MATERIAL AND METHODS. We examined the contribution of KCJN11 mutations to PND in patients from Poland. We sequenced the KCJN11 gene in 7 insulin treated, diabetic patients diagnosed before 6 months (range 1–26 weeks).
RESULTS. We identified three patients with de novo heterozygous missense mutations. Two males, (Pol1 and Pol2) carried the previously described R201H mutation and one female (Pol3) diagnosed at 26 weeks was a carrier of novel mutation R50Q. All three subjects with Kir6.2 mutations presented with severe hyperglycemia at the diagnosis (30–50 mmol/l). There was evidence of clinical heterogeneity: the age of diagnosis was 2, 3 and 26 weeks in Pol1, Pol2, Pol3 respectively; all were born at term with birth weights of 2450, 2700 & 3000 g and insulin requirements varied 0.25, 0.68, 0.1 U/kg. All three patients were successfully transferred to sulphonylurea therapy: Pol1 and Pol2 to sustained-release Glipizide 5 and 30 mg daily, respectively, Pol3 to 0.5 mg glimepiride.
CONCLUSION. We conclude that Kir6.2 mutations are a common cause of PND in European Caucasians and provided the evidence of clinical heterogeneity between mutation carriers. The clinical results are consistent with the novel mutation R50Q being less severe than R201H although variation between patients with R201H suggest there may be other genetic or environmental moderators of phenotype.
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Keywords

diabetes; neonatal diabetes; Kir6.2; sulphonylurea

About this article
Title

Mutation screening in Kir6.2 gene in subjects with permanent neonatal diabetes. Clinical characteristics and the modification of treatment method

Journal

Clinical Diabetology

Issue

Vol 6, No 3 (2005): Practical Diabetology

Pages

115-120

Published online

2005-05-16

Bibliographic record

Diabetologia Praktyczna 2005;6(3):115-120.

Keywords

diabetes
neonatal diabetes
Kir6.2
sulphonylurea

Authors

Tomasz Klupa
Maciej T. Małecki
Joanna Nazim
Marta Ciechanowska
Jerzy Starzyk
Mieczysław Szalecki
Jacek Sieradzki

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