PAX2 mutations in renal-coloboma syndrome: mutational hotspot and germline mosaicism

Eur J Hum Genet. 2000 Nov;8(11):820-6. doi: 10.1038/sj.ejhg.5200539.


The renal-coloboma syndrome (RCS, MIM 120330) is an autosomal dominant disorder caused by PAX2 gene mutations. We screened the entire coding sequence of the PAX2 gene for mutations in nine patients with RCS. We found five heterozygous PAX2 gene mutations: a dinucleotide insertion (2G) at position 619 in one sporadic RCS case, a single nucleotide insertion (619 + G) in three unrelated cases, and a single nucleotide deletion in a familial case. In this familial case, three affected sibs showed a striking ocular phenotypic variability. Each of the sibs carried a 619insG mutation, whilst unaffected parents did not, suggesting the presence of germline mosaicism. Interestingly, the 619insG mutation has been previously reported in several patients and is also responsible for the Pax21Neu mouse mutant, an animal model of human RCS. This study confirms the critical role of the PAX2 gene in human renal and ocular development. In addition, it emphasises the high variability of ocular defects associated with PAX2 mutations ranging from subtle optic disc anomalies to microphthalmia. Finally, the presence of PAX2 germline mosaicism highlights the difficulties associated with genetic counselling for PAX2 mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Coloboma / genetics*
  • Coloboma / pathology
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Family Health
  • Female
  • Germ-Line Mutation
  • Humans
  • Kidney Diseases / genetics*
  • Kidney Diseases / pathology
  • Male
  • Molecular Sequence Data
  • Mosaicism
  • Mutagenesis, Insertional
  • Mutation
  • PAX2 Transcription Factor
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • Sequence Deletion
  • Sequence Homology, Nucleic Acid
  • Syndrome
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • PAX2 Transcription Factor
  • PAX2 protein, human
  • Transcription Factors
  • DNA