title: Novel mutations and a mutational hotspot in the MODY3 gene.
abstract: Maturity-onset diabetes of the young 3 (MODY3) is a type of NIDDM caused by mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha) located on chromosome 12q. We have identified four novel HNF-1alpha missense mutations in MODY3 families. In four additional and unrelated families, we observed an identical insertion mutation that had occurred in a polycytidine tract in exon 4. Among those families, one exhibited a de novo mutation at this location. We propose that instability of this sequence represents a general mutational mechanism in MODY3. We observed no HNF-1alpha mutations among 86 unrelated late-onset diabetic patients with relative insulin deficiency. Hence mutations in this gene appear to be most strongly associated with early-onset diabetes.
authors.affiliation: Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Glucksmann
authors.forename: M
authors.initials: M
authors.lastname: Lehto
authors.forename: O
authors.initials: O
authors.lastname: Tayber
authors.forename: S
authors.initials: S
authors.lastname: Scotti
authors.forename: L
authors.initials: L
authors.lastname: Berkemeier
authors.forename: J C
authors.initials: JC
authors.lastname: Pulido
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: W J
authors.initials: WJ
authors.lastname: Nir
authors.forename: L
authors.initials: L
authors.lastname: Fang
authors.forename: P
authors.initials: P
authors.lastname: Markel
authors.forename: K D
authors.initials: KD
authors.lastname: Munnelly
authors.forename: J
authors.initials: J
authors.lastname: Goranson
authors.forename: M
authors.initials: M
authors.lastname: Orho
authors.forename: B M
authors.initials: BM
authors.lastname: Young
authors.forename: J L
authors.initials: JL
authors.lastname: Whitacre
authors.forename: C
authors.initials: C
authors.lastname: McMenimen
authors.forename: M
authors.initials: M
authors.lastname: Wantman
authors.forename: T
authors.initials: T
authors.lastname: Tuomi
authors.forename: J
authors.initials: J
authors.lastname: Warram
authors.forename: C M
authors.initials: CM
authors.lastname: Forsblom
authors.forename: M
authors.initials: M
authors.lastname: Carlsson
authors.forename: J
authors.initials: J
authors.lastname: Rosenzweig
authors.forename: G
authors.initials: G
authors.lastname: Kennedy
authors.forename: G M
authors.initials: GM
authors.lastname: Duyk
authors.forename: J D
authors.initials: JD
authors.lastname: Thomas
mesh_terms: D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005190:Family; D008040:Genetic Linkage; D006239:Haplotypes; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta