PMID- 10333057
OWN - NLM
STAT- MEDLINE
DCOM- 19990702
LR  - 20190816
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 42
IP  - 5
DP  - 1999 May
TI  - Three new mutations in the hepatocyte nuclear factor-1alpha gene in Japanese
      subjects with diabetes mellitus: clinical features and functional
      characterization.
PG  - 621-6
AB  - AIMS/HYPOTHESIS: Mutations in the hepatocyte nuclear factor-1alpha gene are a
      common cause of the type 3 form of maturity-onset diabetes of the young. We
      examined the clinical features and molecular basis of hepatocyte nuclear
      factor-1alpha (HNF-1alpha) diabetes. METHODS: Thirty-seven Japanese subjects with
      early onset Type II (non-insulin-dependent) diabetes mellitus and 45 with Type I 
      (insulin-dependent) diabetes mellitus were screened for mutations in this gene.
      Functional properties of mutant HNF-1alpha were also investigated. RESULTS: Three
      new mutations [G415R, R272C and A site of the promoter (+ 102G-to-C)] were found.
      Insulin secretion was impaired in the three subjects. Insulin and glucagon
      secretory responses to arginine in the subject with the R272C mutation were also 
      diminished. Molecular biological studies indicated that the G415R mutation
      generated a protein with about 50% of the activity of wild-type HNF-1alpha. The
      R272C mutation had no transactivating or DNA binding activity and acted in a
      dominant negative manner. The + 102 G-to-C mutation in the A site of the promoter
      activity was associated with an increase in promoter activity and it had 42-75%
      more activity than the wild-type sequence. CONCLUSION/INTERPRETATION: Mutations
      in the HNF-1alpha gene may affect the normal islet function by different
      molecular mechanisms.
FAU - Yoshiuchi, I
AU  - Yoshiuchi I
AD  - Department of Internal Medicine and Molecular Science, Graduate School of
      Medicine, Osaka University, Suita, Japan.
FAU - Yamagata, K
AU  - Yamagata K
FAU - Yang, Q
AU  - Yang Q
FAU - Iwahashi, H
AU  - Iwahashi H
FAU - Okita, K
AU  - Okita K
FAU - Yamamoto, K
AU  - Yamamoto K
FAU - Oue, T
AU  - Oue T
FAU - Imagawa, A
AU  - Imagawa A
FAU - Hamaguchi, T
AU  - Hamaguchi T
FAU - Yamasaki, T
AU  - Yamasaki T
FAU - Horikawa, Y
AU  - Horikawa Y
FAU - Satoh, T
AU  - Satoh T
FAU - Nakajima, H
AU  - Nakajima H
FAU - Miyazaki, J
AU  - Miyazaki J
FAU - Higashiyama, S
AU  - Higashiyama S
FAU - Miyagawa, J
AU  - Miyagawa J
FAU - Namba, M
AU  - Namba M
FAU - Hanafusa, T
AU  - Hanafusa T
FAU - Matsuzawa, Y
AU  - Matsuzawa Y
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (C-Peptide)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HNF1A protein, human)
RN  - 0 (HNF1B protein, human)
RN  - 0 (Hepatocyte Nuclear Factor 1-alpha)
RN  - 0 (Insulin)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 126548-29-6 (Hepatocyte Nuclear Factor 1)
RN  - 138674-15-4 (Hepatocyte Nuclear Factor 1-beta)
RN  - 9007-49-2 (DNA)
RN  - 9007-92-5 (Glucagon)
RN  - 94ZLA3W45F (Arginine)
SB  - IM
MH  - Adult
MH  - Arginine
MH  - C-Peptide/blood/urine
MH  - DNA/metabolism
MH  - *DNA-Binding Proteins
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Female
MH  - Glucagon/blood/metabolism
MH  - Glucose Tolerance Test
MH  - Hepatocyte Nuclear Factor 1
MH  - Hepatocyte Nuclear Factor 1-alpha
MH  - Hepatocyte Nuclear Factor 1-beta
MH  - Humans
MH  - Insulin/blood/metabolism
MH  - Insulin Secretion
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - *Nuclear Proteins
MH  - Promoter Regions, Genetic
MH  - Transcription Factors/*genetics
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 - 10.1007/s001250051204 [doi]
PST - ppublish
SO  - Diabetologia. 1999 May;42(5):621-6. doi: 10.1007/s001250051204.