Homonucleotide expansion and contraction mutations of PAX2 and inclusion of Chiari 1 malformation as part of Renal-Coloboma syndrome

Lisa A. Schimmenti, Heather H. Shim, Jonathan D. Wirtschafter, Valerie A. Panzarino, Clifford E. Kashtan, Susan J. Kirkpatrick, David S. Wargowski, Thomas D. France, Eduard Michel, William B. Dobyns

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Renal-Coloboma syndrome, an autosomal dominant disorder characterized by colobomatous eye defects, vesicoureteral reflux, and abnormal kidneys, results from mutations in PAX2. The purpose of this study was to identify mutations in PAX2 and understand the associated patient phenotypes. We report a severely affected girl and a mildly affected mother and daughter, all of whom have PAX2 homoguanine tract (7 G) missense mutations. The mother and daughter have optic nerve colobomas and the daughter has vesicoureteral reflux. The severely affected girl developed renal failure and has bilateral colobomatous eye defects. Additionally, this girl developed hydrocephalus associated with platybasia and a Chiari 1 malformation. We examined genomic DNA from these individuals by SSCP and sequencing. The mother and daughter had a novel mutation: a contraction in a string of 7 G's to 6 G's in one allele of PAX2, leading to a premature stop codon two amino acids downstream. The severely affected girl had an expansion to 8 G's, leading to a premature stop codon 27 amino acids downstream. The 8 G expansion has been found in other patients without brain anomalies and has occurred spontaneously in a mouse model, PAX2(1Neu). We expand the known phenotype associated with mutations in PAX2 to include brain malformations. The homoguanine tract in PAX2 is a hot spot for spontaneous expansion or contraction mutations and demonstrates the importance of homonucleotide tract mutations in human malformation syndromes.

Original languageEnglish (US)
Pages (from-to)369-376
Number of pages8
JournalHuman mutation
Issue number5
StatePublished - 1999


  • Coloboma
  • Expansion/contraction mutations
  • Homonucleotide
  • Pax2
  • Renal anomalies
  • Renal- Coloboma syndrome


Dive into the research topics of 'Homonucleotide expansion and contraction mutations of PAX2 and inclusion of Chiari 1 malformation as part of Renal-Coloboma syndrome'. Together they form a unique fingerprint.

Cite this