title: De novo double mutation in PAX6 and mtDNA tRNA(Lys) associated with atypical aniridia and mitochondrial disease.
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.
authors.affiliation: Department of Biology, Chemistry and Pharmacy, Free University Berlin, Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Brinckmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Rüther
authors.forename: Kathleen
authors.initials: K
authors.lastname: Williamson
authors.forename: Birgit
authors.initials: B
authors.lastname: Lorenz
authors.forename: Barbara
authors.initials: B
authors.lastname: Lucke
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Frans
authors.initials: F
authors.lastname: Trijbels
authors.forename: Antoon
authors.initials: A
authors.lastname: Janssen
authors.forename: Markus
authors.initials: M
authors.lastname: Schuelke
mesh_terms: D000293:Adolescent; D015783:Aniridia / Q000175:diagnosis / Q000235:genetics*; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005347:Fibroblasts; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics*; D009132:Muscles; D009154:Mutation; D010101:Oxygen Consumption; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D012357:RNA, Transfer, Lys / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012357:RNA, Transfer, Lys; D012097:Repressor Proteins