De novo double mutation in PAX6 and mtDNA tRNA(Lys) associated with atypical aniridia and mitochondrial disease

Anja Brinckmann, Klaus Rüther, Kathleen Williamson, Birgit Lorenz, Barbara Lucke, Peter Nürnberg, Frans Trijbels, Antoon Janssen, Markus Schuelke

Research output: Contribution to journalArticlepeer-review

Abstract

We report on the clinical, molecular and biochemical findings of a patient with the rare event (<4.02 x 10(-9) per generation) of coinciding de novo mutations in the nuclear PAX6 (c.1252-1267del16) and the mitochondrial mt.RNA (Lys) (8347A-->G) genes. The boy suffers from exercise intolerance, ptosis, nystagmus, macular hypoplasia and anterior segment abnormalities evocative of Axenfeld-Rieger anomaly. The PAX6 mutation is predicted to cause haploinsufficiency. The novel mt.RNA (Lys) mutation is located close to the classic myoclonic epilepsy with ragged-red-fibers mutation, but the patient exhibits neither myoclonic epilepsy nor ragged-red-fibers. The degree of mutant mtDNA heteroplasmy, as determined by a very accurate pyrosequencing assay, varies between 31% (muscle) and 38% (fibroblasts). We discuss a potential effect of the PAX6 mutation on the mtDNA mutation rate.

Original languageEnglish
Pages (from-to)163-8
Number of pages6
JournalJournal of Molecular Medicine
Volume85
Issue number2
DOIs
Publication statusPublished - Feb 2007

Keywords

  • Adolescent
  • Aniridia/diagnosis
  • Cells, Cultured
  • DNA, Mitochondrial/genetics
  • Eye Proteins/genetics
  • Fibroblasts
  • Homeodomain Proteins/genetics
  • Humans
  • Male
  • Mitochondrial Diseases/diagnosis
  • Muscles
  • Mutation
  • Oxygen Consumption
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors/genetics
  • RNA, Transfer, Lys/genetics
  • Repressor Proteins/genetics

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