Recent advances in the genetics of mitochondrial encephalopathies.
Mitochondrial encephalopathy, the most common neurometabolic disorder, may be caused by mutations in approximately 100 different genes and may present with various symptoms, such as seizures, ataxia, myopathy, cognitive impairment, blindness, and stroke. Fewer than 50% of patients with mitochondrial encephalopathy receive a molecular diagnosis, primarily because of the large degree of clinical and genetic heterogeneity among patients and the limited knowledge of the genes involved in mitochondrial function. Here we review the most recent discoveries of genes associated with mitochondrial disease with variable neuropathology. All these genes have been identified via homozygosity mapping or linkage analysis; however, advances in sequencing technology indicate that the future of genetic diagnosis and disease gene discovery likely lies in high-throughput sequencing.
Tucker
Elena J
EJ
Murdoch Childrens Research Institute, The Royal Children's Hospital, 10th Floor, Flemington Road, Parkville, Victoria, 3052, Australia. e.tucker3@pgrad.unimelb.edu.au
Compton
Alison G
AG
Thorburn
David R
DR
D050259:Genes, Mitochondrial; D005838:Genotype; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000235:genetics; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation; D010085:Oxidative Phosphorylation; D010641:Phenotype
D024101:Mitochondrial Proteins
Nat Genet. 2009 May;41(5):510-2
19399033
Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19096-101
19861545
J Inherit Metab Dis. 2004;27(3):349-62
15190193
Nat Genet. 2009 Jun;41(6):654-6
19465911
Eur J Hum Genet. 2007 Jul;15(7):779-83
17426723
Nat Genet. 2006 May;38(5):576-82
16582907
Nat Genet. 2009 Jul;41(7):833-7
19503089
Nature. 1988 Feb 25;331(6158):717-9
2830540
J Med Genet. 2010 Aug;47(8):507-12
19542079
Am J Hum Genet. 2008 Aug;83(2):254-60
18674747
Biochim Biophys Acta. 2009 May;1787(5):529-32
19103153
Am J Hum Genet. 2008 May;82(5):1211-6
18439546
Nat Med. 2009 Feb;15(2):200-5
19136963
N Engl J Med. 2009 Feb 5;360(6):642-4
19196685
Am J Med Genet. 2001 Spring;106(1):18-26
11579421
N Engl J Med. 2009 Feb 5;360(6):640-2
19196684
Science. 2009 Aug 28;325(5944):1139-42
19628817
Nat Rev Genet. 2010 Jan;11(1):31-46
19997069
Cell Metab. 2006 Jan;3(1):9-13
16399500
J Med Genet. 2003 Dec;40(12):896-9
14684687
Am J Hum Genet. 2009 Mar;84(3):412-7
19268275
Brain. 2003 Aug;126(Pt 8):1905-12
12805096
Am J Hum Genet. 2009 Jun;84(6):718-27
19463981
Am J Hum Genet. 2008 Oct;83(4):468-78
18940309
Am J Hum Genet. 2008 Jun;82(6):1306-15
18513682
Nat Genet. 2009 May;41(5):535-43
19377476
Brain. 2009 Jan;132(Pt 1):136-46
19015156
Am J Hum Genet. 2008 Sep;83(3):415-23
18771761
Am J Hum Genet. 2008 Jun;82(6):1281-9
18499082
Am J Hum Genet. 2009 Sep;85(3):401-7
19732863
Science. 1988 Dec 9;242(4884):1427-30
3201231
Biochem Biophys Res Commun. 1998 Oct 29;251(3):883-7
9791004
Am J Hum Genet. 2009 May;84(5):558-66
19375058
Nat Genet. 1995 Oct;11(2):144-9
7550341
Nat Genet. 2008 Nov;40(11):1288-90
18953340