The spectrum of ABCC8 mutations in Norwegian patients with congenital hyperinsulinism of infancy

T Sandal, L B Laborie, K Brusgaard, S A Eide, H B T Christesen, O Søvik, P R Njølstad, A Molven

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2009-May
OriginalsprogEngelsk
TidsskriftClinical Genetics
Vol/bind75
Udgave nummer5
Sider (fra-til)440-8
Antal sider8
ISSN0009-9163
StatusUdgivet - 1. maj 2009

Fingeraftryk

Congenital Hyperinsulinism
Mutation
Sulfonylurea Receptors
Scandinavian and Nordic Countries
Pancreatic Diseases
Insulin-Secreting Cells
Norway
Homeostasis

Citer dette

Sandal, T ; Laborie, L B ; Brusgaard, K ; Eide, S A ; Christesen, H B T ; Søvik, O ; Njølstad, P R ; Molven, A. / The spectrum of ABCC8 mutations in Norwegian patients with congenital hyperinsulinism of infancy. I: Clinical Genetics. 2009 ; Bind 75, Nr. 5. s. 440-8.
@article{615c29000bff11dfaefb000ea68e967b,
title = "The spectrum of ABCC8 mutations in Norwegian patients with congenital hyperinsulinism of infancy",
abstract = "Potassium channels in the plasma membrane of the pancreatic beta cells are critical in maintaining glucose homeostasis by responding to ATP and coupling metabolic changes to insulin secretion. These channels consist of subunits denoted the sulfonylurea receptor SUR1 and the inwardly rectifying ion channel KIR6.2, which are encoded by the genes ABCC8 and KCNJ11, respectively. Activating mutations in the subunit genes can result in monogenic diabetes, whereas inactivating mutations are the most common cause of congenital hyperinsulinism of infancy (CHI). Twenty-six Norwegian probands with CHI were analyzed for alterations in ABCC8 and KCNJ11. Fifteen probands (58{\%}) had mutations in the ABCC8 gene. Nine patients were homozygous or compound heterozygous for the mutations, indicating diffuse pancreatic disease. In five patients, heterozygous and paternally inherited mutations were found, suggesting focal disease. One patient had a de novo mutation likely to cause a milder, dominant form of CHI. Altogether, 16 different ABCC8 mutations (including the novel alterations W231R, C267X, IVS6-3C>G, I462V, Q917X and T1531A) were identified. The mutations IVS10+1G>T, R1493W and V21D occurred in five, three and two families, respectively. KCNJ11 mutations were not found in any patients. Based on our mutation screening, we estimate the minimum birth prevalence of ABCC8-CHI in Norway to 1:70,000 during the past decade. Our results considerably extend the knowledge of the molecular genetics behind CHI in Scandinavia.",
keywords = "ATP-Binding Cassette Transporters, Cohort Studies, Female, Genetic Testing, Humans, Infant, Newborn, Male, Mutation, Norway, Pedigree, Persistent Hyperinsulinemia Hypoglycemia of Infancy, Potassium Channels, Inwardly Rectifying, Receptors, Drug",
author = "T Sandal and Laborie, {L B} and K Brusgaard and Eide, {S A} and Christesen, {H B T} and O S{\o}vik and Nj{\o}lstad, {P R} and A Molven",
year = "2009",
month = "5",
day = "1",
language = "English",
volume = "75",
pages = "440--8",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",
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Sandal, T, Laborie, LB, Brusgaard, K, Eide, SA, Christesen, HBT, Søvik, O, Njølstad, PR & Molven, A 2009, 'The spectrum of ABCC8 mutations in Norwegian patients with congenital hyperinsulinism of infancy', Clinical Genetics, bind 75, nr. 5, s. 440-8.

The spectrum of ABCC8 mutations in Norwegian patients with congenital hyperinsulinism of infancy. / Sandal, T; Laborie, L B; Brusgaard, K; Eide, S A; Christesen, H B T; Søvik, O; Njølstad, P R; Molven, A.

I: Clinical Genetics, Bind 75, Nr. 5, 01.05.2009, s. 440-8.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The spectrum of ABCC8 mutations in Norwegian patients with congenital hyperinsulinism of infancy

AU - Sandal, T

AU - Laborie, L B

AU - Brusgaard, K

AU - Eide, S A

AU - Christesen, H B T

AU - Søvik, O

AU - Njølstad, P R

AU - Molven, A

PY - 2009/5/1

Y1 - 2009/5/1

N2 - Potassium channels in the plasma membrane of the pancreatic beta cells are critical in maintaining glucose homeostasis by responding to ATP and coupling metabolic changes to insulin secretion. These channels consist of subunits denoted the sulfonylurea receptor SUR1 and the inwardly rectifying ion channel KIR6.2, which are encoded by the genes ABCC8 and KCNJ11, respectively. Activating mutations in the subunit genes can result in monogenic diabetes, whereas inactivating mutations are the most common cause of congenital hyperinsulinism of infancy (CHI). Twenty-six Norwegian probands with CHI were analyzed for alterations in ABCC8 and KCNJ11. Fifteen probands (58%) had mutations in the ABCC8 gene. Nine patients were homozygous or compound heterozygous for the mutations, indicating diffuse pancreatic disease. In five patients, heterozygous and paternally inherited mutations were found, suggesting focal disease. One patient had a de novo mutation likely to cause a milder, dominant form of CHI. Altogether, 16 different ABCC8 mutations (including the novel alterations W231R, C267X, IVS6-3C>G, I462V, Q917X and T1531A) were identified. The mutations IVS10+1G>T, R1493W and V21D occurred in five, three and two families, respectively. KCNJ11 mutations were not found in any patients. Based on our mutation screening, we estimate the minimum birth prevalence of ABCC8-CHI in Norway to 1:70,000 during the past decade. Our results considerably extend the knowledge of the molecular genetics behind CHI in Scandinavia.

AB - Potassium channels in the plasma membrane of the pancreatic beta cells are critical in maintaining glucose homeostasis by responding to ATP and coupling metabolic changes to insulin secretion. These channels consist of subunits denoted the sulfonylurea receptor SUR1 and the inwardly rectifying ion channel KIR6.2, which are encoded by the genes ABCC8 and KCNJ11, respectively. Activating mutations in the subunit genes can result in monogenic diabetes, whereas inactivating mutations are the most common cause of congenital hyperinsulinism of infancy (CHI). Twenty-six Norwegian probands with CHI were analyzed for alterations in ABCC8 and KCNJ11. Fifteen probands (58%) had mutations in the ABCC8 gene. Nine patients were homozygous or compound heterozygous for the mutations, indicating diffuse pancreatic disease. In five patients, heterozygous and paternally inherited mutations were found, suggesting focal disease. One patient had a de novo mutation likely to cause a milder, dominant form of CHI. Altogether, 16 different ABCC8 mutations (including the novel alterations W231R, C267X, IVS6-3C>G, I462V, Q917X and T1531A) were identified. The mutations IVS10+1G>T, R1493W and V21D occurred in five, three and two families, respectively. KCNJ11 mutations were not found in any patients. Based on our mutation screening, we estimate the minimum birth prevalence of ABCC8-CHI in Norway to 1:70,000 during the past decade. Our results considerably extend the knowledge of the molecular genetics behind CHI in Scandinavia.

KW - ATP-Binding Cassette Transporters

KW - Cohort Studies

KW - Female

KW - Genetic Testing

KW - Humans

KW - Infant, Newborn

KW - Male

KW - Mutation

KW - Norway

KW - Pedigree

KW - Persistent Hyperinsulinemia Hypoglycemia of Infancy

KW - Potassium Channels, Inwardly Rectifying

KW - Receptors, Drug

M3 - Journal article

VL - 75

SP - 440

EP - 448

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 5

ER -