PMID- 10334322
OWN - NLM
STAT- MEDLINE
DCOM- 19990610
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 48
IP  - 2
DP  - 1999 Feb
TI  - A point mutation inactivating the sulfonylurea receptor causes the severe form of
      persistent hyperinsulinemic hypoglycemia of infancy in Finland.
PG  - 408-15
AB  - Mutations in genes encoding the ATP-regulated potassium (K(ATP)) channels of the 
      pancreatic beta-cell (SUR1 and Kir6.2) are the major known cause of persistent
      hyperinsulinemic hypoglycemia of infancy (PHHI). We collected all cases of PHHI
      diagnosed in Finland between 1983 and 1997 (n = 24). The overall incidence was
      1:40,400, but in one area of Central Finland it was as high as 1:3,200. Haplotype
      analysis using polymorphic markers spanning the SUR1/Kir6.2 gene cluster
      confirmed linkage to the 11p region. Sequence analysis revealed a novel point
      mutation in exon 4 of SUR1, predicting a valine to aspartic acid change at amino 
      acid 187 (V187D). Of the total cases, 15 affected individuals harbored this
      mutation in heterozygous or homozygous form, and all of these had severe
      hyperinsulinemia that responded poorly to medical treatment and required subtotal
      pancreatectomy. No K(ATP) channel activity was observed in beta-cells isolated
      from a homozygous patient or after coexpression of recombinant Kir6.2 and SUR1
      carrying the V187D mutation. Thus, the mutation produces a nonfunctional channel 
      and, thereby, continuous insulin secretion. This unique SUR1 mutation explains
      the majority of PHHI cases in Finland and is strongly associated with a severe
      form of the disease. These findings provide diagnostic and prognostic utility for
      suspected PHHI patients.
FAU - Otonkoski, T
AU  - Otonkoski T
AD  - Transplantation Laboratory, Haartman Institute,and University of Helsinki,
      Finland. timo.otonkoski@helsinki.fi
FAU - Ammala, C
AU  - Ammala C
FAU - Huopio, H
AU  - Huopio H
FAU - Cote, G J
AU  - Cote GJ
FAU - Chapman, J
AU  - Chapman J
FAU - Cosgrove, K
AU  - Cosgrove K
FAU - Ashfield, R
AU  - Ashfield R
FAU - Huang, E
AU  - Huang E
FAU - Komulainen, J
AU  - Komulainen J
FAU - Ashcroft, F M
AU  - Ashcroft FM
FAU - Dunne, M J
AU  - Dunne MJ
FAU - Kere, J
AU  - Kere J
FAU - Thomas, P M
AU  - Thomas PM
LA  - eng
GR  - HD-28820/HD/NICHD NIH HHS/United States
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (ABCC8 protein, human)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Inwardly Rectifying)
RN  - 0 (Receptors, Drug)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Sulfonylurea Receptors)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - AIM
SB  - IM
MH  - *ATP-Binding Cassette Transporters
MH  - Adenosine Triphosphate/physiology
MH  - Animals
MH  - Electrophysiology
MH  - Female
MH  - Finland
MH  - Haplotypes/genetics
MH  - Humans
MH  - Hyperinsulinism/*complications/*genetics
MH  - Hypoglycemia/*etiology/*genetics
MH  - Incidence
MH  - Infant
MH  - Infant, Newborn
MH  - Islets of Langerhans/metabolism
MH  - Male
MH  - Mutation/genetics
MH  - Point Mutation/*genetics
MH  - Potassium Channels/*genetics/metabolism/physiology
MH  - *Potassium Channels, Inwardly Rectifying
MH  - Receptors, Drug/*genetics
MH  - Recombinant Proteins
MH  - Sulfonylurea Receptors
MH  - Xenopus laevis
EDAT- 1999/05/20 00:00
MHDA- 1999/05/20 00:01
CRDT- 1999/05/20 00:00
PHST- 1999/05/20 00:00 [pubmed]
PHST- 1999/05/20 00:01 [medline]
PHST- 1999/05/20 00:00 [entrez]
AID - 10.2337/diabetes.48.2.408 [doi]
PST - ppublish
SO  - Diabetes. 1999 Feb;48(2):408-15. doi: 10.2337/diabetes.48.2.408.