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

Item Type:	Article
Title:	De novo double mutation in PAX6 and mtDNA tRNA ( Lys ) associated with atypical aniridia and mitochondrial disease
Creators Name:	Brinckmann, A. and Ruether, K. and Williamson, K. and Lorenz, B. and Lucke, B. and Nuernberg, P. and Trijbels, F. and Janssen, A. and Schuelke, M.
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.
Keywords:	mtDNA, Heteroplasmy, PAX6, Ptosis, Nystagmus, Pyrosequencing
Source:	Journal of Molecular Medicine
ISSN:	0946-2716
Publisher:	Springer
Volume:	85
Page Range:	163-168
Date:	February 2007
Official Publication:	https://doi.org/10.1007/s00109-006-0112-y
PubMed:	View item in PubMed

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