A case of novel de novo paired box gene 6 (PAX6) mutation with early-onset diabetes mellitus and aniridia

Diabet Med. 2005 May;22(5):641-4. doi: 10.1111/j.1464-5491.2005.01469.x.


Background: Paired box gene 6 (PAX6) is a transcription factor involved in eye development. Mutations of PAX6 cause congenital eye anomalies, such as aniridia. PAX6 is also involved in the development of the endocrine pancreas, and reported to be a genetic factor common to aniridia and glucose intolerance, although the latter is usually mild. Here, we describe a case of PAX6 mutation with early-onset diabetes mellitus.

Case report: A 27-year-old woman was referred to our clinic. She was diagnosed having diabetes at the age of 15 with negative glutamic acid decarboxylase (GAD) antibody. Insulin treatment was started at age 24. Because she had aniridia, PAX6 gene mutation was investigated and a heterozygous 2-bp deletion (c.402del2) was identified. Her parents did not have aniridia and PAX6 mutations. Heterozygous PAX6 mutation may cause glucose intolerance. However, cases of early-onset diabetes mellitus have not been reported. Her parents did not have diabetes, but their insulinogenic indices were low (0.25 and 0.3, respectively). We thought her early-onset diabetes was partly as a result of PAX6 mutation and partly because of an unknown insulin secretory defect inherited from her parents. We could not find any mutations in HNF-1alpha, -1beta, -4alpha, IPF-1, ISL-1, BEAT2/NeuroD1, PAX4, and amylin genes.

Conclusions: We report a case of PAX6 gene mutation with early-onset diabetes mellitus and aniridia. Low insulin secretory capacity in her parents suggested that her insulin secretory defect is as a result of not only PAX6 mutation but other genetic factors inherited from her parents.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aniridia / genetics*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / genetics*
  • Eye Proteins / genetics*
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Mutation / genetics*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Repressor Proteins / genetics*
  • Sequence Deletion


  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Repressor Proteins