PMID- 24642958
OWN - NLM
STAT- MEDLINE
DCOM- 20150113
LR  - 20160519
IS  - 1663-2826 (Electronic)
IS  - 1663-2818 (Linking)
VI  - 81
IP  - 4
DP  - 2014
TI  - A family with a novel termination mutation in hepatic nuclear factor 1alpha in 
      maturity-onset diabetes of the young type 3 which is unresponsive to 
      sulphonylurea therapy.
PG  - 280-4
LID - 10.1159/000356925 [doi]
AB  - BACKGROUND: Maturity-onset diabetes of the young (MODY) is a monogenic form of 
      diabetes mellitus. AIMS: To identify the genetic basis in a family with 3 
      generations of diabetes and to assess the concordance between the genotype and 
      phenotype. METHODS: A molecular analysis was performed on genomic DNA using 
      polymerase chain reaction, denaturing gradient gel electrophoresis, and 
      sequencing. A mixed-meal tolerance test (MMTT) was performed with/without 
      glibenclamide. Abdominal ultrasonography was performed on all family members with 
      diabetes due to the location of the mutation. RESULTS: A novel c.618G>A, p.W206X 
      termination mutation was identified in the hepatic nuclear factor 1alpha (HNF1alpha) 
      gene. The mutation was identified in the proband and 8 of the 14 family members 
      tested. An MMTT stimulus (+/-2.5 and 5 mg glibenclamide) produced a similar glucose 
      profile and C-peptide graph in both the obese proband and her nonobese mother, 
      showing no effect of the glibenclamide. No evidence of liver adenomas was found 
      in the abdominal ultrasonography. CONCLUSIONS: We described a novel c.618G>A, 
      p.W206X mutation in HNF1alpha associated with MODY 3 but not with hepatocellular 
      adenoma. In contradistinction to most MODY 3 mutations, treatment with 
      sulphonylurea was found to be a clinically ineffective alternative to insulin 
      therapy.
FAU - Demol, S
AU  - Demol S
AD  - The Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, 
      National Center for Childhood Diabetes, Schneider Children's Medical Center of 
      Israel, Petach Tikva, Israel.
FAU - Lebenthal, Y
AU  - Lebenthal Y
FAU - Bar-Meisels, M
AU  - Bar-Meisels M
FAU - Phillip, M
AU  - Phillip M
FAU - Gat-Yablonski, G
AU  - Gat-Yablonski G
FAU - Gozlan, Y
AU  - Gozlan Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140312
PL  - Switzerland
TA  - Horm Res Paediatr
JT  - Hormone research in paediatrics
JID - 101525157
RN  - 0 (HNF1A protein, human)
RN  - 0 (Hepatocyte Nuclear Factor 1-alpha)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Sulfonylurea Compounds)
RN  - Maturity-Onset Diabetes of the Young, Type 3
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Child
MH  - Diabetes Mellitus, Type 2/drug therapy/*genetics
MH  - Female
MH  - Hepatocyte Nuclear Factor 1-alpha/*genetics
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Insulin/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Pedigree
MH  - Phenotype
MH  - Sulfonylurea Compounds/*therapeutic use
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2014/03/20 06:00
MHDA- 2015/01/15 06:00
CRDT- 2014/03/20 06:00
PHST- 2013/05/03 00:00 [received]
PHST- 2013/10/22 00:00 [accepted]
PHST- 2014/03/20 06:00 [entrez]
PHST- 2014/03/20 06:00 [pubmed]
PHST- 2015/01/15 06:00 [medline]
AID - 000356925 [pii]
AID - 10.1159/000356925 [doi]
PST - ppublish
SO  - Horm Res Paediatr. 2014;81(4):280-4. doi: 10.1159/000356925. Epub 2014 Mar 12.