Novel mutations and a mutational hotspot in the MODY3 gene.
- M A Glucksmann,
- M Lehto,
- O Tayber,
- S Scotti,
- L Berkemeier,
- J C Pulido,
- Y Wu,
- W J Nir,
- L Fang,
- P Markel,
- K D Munnelly,
- J Goranson,
- M Orho,
- B M Young,
- J L Whitacre,
- C McMenimen,
- M Wantman,
- T Tuomi,
- J Warram,
- C M Forsblom,
- M Carlsson,
- J Rosenzweig,
- G Kennedy,
- G M Duyk and
- J D Thomas
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.
