Neonatal diabetes mellitus and neonatal polycystic, dysplastic kidneys: Phenotypically discordant recurrence of a mutation in the hepatocyte nuclear factor-1beta gene due to germline mosaicism

J Clin Endocrinol Metab. 2004 Jun;89(6):2905-8. doi: 10.1210/jc.2003-031828.


Mutations in the gene coding for hepatocyte nuclear factor-1beta (HNF-1beta) have been known to cause a form of maturity-onset diabetes of the young (MODY5), which is usually characterized by dominantly inherited adolescence-onset diabetes mellitus associated with renal cysts. This report, however, describes recurrence of a novel missense mutation in the HNF-1beta gene, S148W (C443G), in two sibs, one with neonatal diabetes mellitus and the other with neonatal polycystic, dysplastic kidneys leading to early renal failure. The former patient had only a few small renal cysts with normal renal functions, and the latter had only a transient episode of hyperglycemia, which resolved spontaneously. Interestingly, both parents were clinically unaffected, and PCR restriction fragment length polymorphism analysis showed that the mother was a low-level mosaic of normal and mutant HNF-1beta, which suggested that the recurrence was caused by germline mosaicism. This is the first report of permanent neonatal diabetes mellitus caused by a mutation of the HNF-1beta gene as well as the first report of germline mosaicism of this gene. In addition, the two cases described here show that additional factors, genetic or environmental, can have a significant influence on the phenotypic expression of HNF-1beta mutations.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genotype
  • Germ-Line Mutation*
  • Hepatocyte Nuclear Factor 1-beta
  • Humans
  • Infant, Newborn
  • Infant, Newborn, Diseases / genetics*
  • Male
  • Mosaicism
  • Mutation, Missense
  • Phenotype
  • Polycystic Kidney Diseases / complications
  • Polycystic Kidney Diseases / genetics*
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • HNF1B protein, human
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1-beta