De novo double mutation in PAX6 and mtDNA tRNA Lys associated with atypical aniridia and mitochondrial disease
We report on the clinical, molecular and biochemical findings of a patient with the rare event (<4.02 × 10-9 per generation) of coinciding de novo mutations in the nuclear PAX6 (c.1252-1267del16) and the mitochondrial mt.RNA Lys (8347A[arrow right]G) genes. The boy suffers from exercise intoleran...
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| Published in | Journal of molecular medicine (Berlin, Germany) Vol. 85; no. 2; pp. 163 - 168 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Springer Nature B.V
01.02.2007
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| Online Access | Get full text |
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| Abstract | We report on the clinical, molecular and biochemical findings of a patient with the rare event (<4.02 × 10-9 per generation) of coinciding de novo mutations in the nuclear PAX6 (c.1252-1267del16) and the mitochondrial mt.RNA Lys (8347A[arrow right]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. |
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| AbstractList | We report on the clinical, molecular and biochemical findings of a patient with the rare event (<4.02 × 10-9 per generation) of coinciding de novo mutations in the nuclear PAX6 (c.1252-1267del16) and the mitochondrial mt.RNA Lys (8347A[arrow right]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. |
| Author | Brinckmann, Anja Nürnberg, Peter Lucke, Barbara Janssen, Antoon Trijbels, Frans Rüther, Klaus Williamson, Kathleen Lorenz, Birgit Schuelke, Markus |
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| CitedBy_id | crossref_primary_10_3109_19401736_2012_760072 crossref_primary_10_3724_SP_J_1005_2008_01301 crossref_primary_10_1017_cjn_2017_211 crossref_primary_10_1002_mgg3_47 crossref_primary_10_1136_jmedgenet_2016_103876 crossref_primary_10_1371_journal_pone_0013513 crossref_primary_10_1111_j_1749_6632_2010_05626_x crossref_primary_10_3109_02713683_2012_688165 crossref_primary_10_1002_elps_200900325 crossref_primary_10_1097_WCO_0b013e3282efeb3b |
| Cites_doi | 10.1038/ng1192-232 10.1186/1471-2156-6-27 10.1034/j.1399-0004.2001.600210.x 10.1093/emboj/20.17.4794 10.1002/ajmg.1392 10.2337/diabetes.51.11.3331 10.1006/mcpr.1994.1006 10.1002/elps.200290023 10.1093/nar/gki079 10.1002/ana.10151 10.1093/hmg/11.10.1161 10.1038/npg.els.0001768 10.1038/90042 10.1136/jmg.39.1.16 10.1016/S1471-4914(02)02298-0 10.1177/153537020222700901 10.1006/dbio.1998.9028 10.1093/clinchem/43.7.1241 10.1038/82565 10.1093/molbev/msi141 |
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| Title | De novo double mutation in PAX6 and mtDNA tRNA Lys associated with atypical aniridia and mitochondrial disease |
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