The pathogenic m.3243A>T mitochondrial DNA mutation is associated with a variable neurological phenotype

被引：4

作者：

Alston, Charlotte L. ^{[1
]}

Bender, Andreas ^{[2
]}

Hargreaves, Iain P. ^{[3
]}

Mundy, Helen ^{[4
]}

Deshpande, Charulata ^{[5
]}

Klopstock, Thomas ^{[2
,6
]}

McFarland, Robert ^{[1
]}

Horvath, Rita ^{[1
]}

Taylor, Robert W. ^{[1
]}

机构：

[1] Newcastle Univ, Mitochondrial Res Grp, Inst Ageing & Hlth, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[2] Univ Munich, Dept Neurol, Klinikum Grosshadern, D-81377 Munich, Germany

[3] Natl Hosp Neurol & Neurosurg, Neurometab Unit, London WC1N 3BG, England

[4] Guys & St Thomas NHS Fdn Trust, Ctr Inherited Metab Dis, London, England

[5] Guys & St Thomas NHS Fdn Trust, Dept Clin Genet, London, England

[6] Univ Munich, Friedrich Baur Inst, Dept Neurol, Klinikum Innenstadt, D-80336 Munich, Germany

来源：

NEUROMUSCULAR DISORDERS | 2010年 / 20卷 / 06期

基金：

英国惠康基金;

关键词：

Mitochondrial DNA; m.3243; CPEO; Pathogenicity; Single fibres; HUMAN-DISEASE; MTDNA; DIAGNOSIS; CELLS;

D O I：

10.1016/j.nmd.2010.04.003

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The m.3243A>G point mutation in the mitochondrial tRNA(Leu(UUR)) (MTTL1) gene is a common cause of mitochondrial DNA disease and is associated with a variety of clinical presentations. A different mutation occurring at the same site - an m.3243A>T transversion - is less prevalent, but has previously been observed in two patients with encephalopathy and lactic acidosis. We report the investigations of a further two patients with the m.3243A>T mutation who presented with either a chronic progressive external ophthalmoplegia (CPEO) phenotype or sensorineural hearing loss, with single fibre mutation studies confirming segregation of the m.3243A>T mutation with COX deficiency. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：403 / 406

页数：4

共 22 条

[1] Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA [J].

Andrews, RM ;

Kubacka, I ;

Chinnery, PF ;

Lightowlers, RN ;

Turnbull, DM ;

Howell, N .

NATURE GENETICS, 1999, 23 (02) :147-147

[2] Nuclear genetic control of mitochondrial DNA segregation [J].

Battersby, BJ ;

Loredo-Osti, JC ;

Shoubridge, EA .

NATURE GENETICS, 2003, 33 (02) :183-186

[3] Gastrointestinal tract involvement associated with the 3243A>G mitochondrial DNA mutation [J].

Betts, J. ;

Barron, M. J. ;

Needham, S. J. ;

Schaefer, A. M. ;

Taylor, R. W. ;

Turnbull, D. M. .

NEUROLOGY, 2008, 70 (15) :1290-1292

[4] Novel mutations in the TK2 gene associated with fatal mitochondrial DNA depletion myopathy [J].

Blakely, Emma ;

He, Langping ;

Gardner, Julie L. ;

Hudson, Gavin ;

Walter, John ;

Hughes, Imelda ;

Turnbull, Douglass M. ;

Taylor, Robert W. .

NEUROMUSCULAR DISORDERS, 2008, 18 (07) :557-560

[5]

Chinnery PF, 1999, AM J MED GENET, V85, P498

[6] MELAS MUTATION IN MTDNA BINDING-SITE FOR TRANSCRIPTION TERMINATION FACTOR CAUSES DEFECTS IN PROTEIN-SYNTHESIS AND IN RESPIRATION BUT NO CHANGE IN LEVELS OF UPSTREAM AND DOWNSTREAM MATURE TRANSCRIPTS [J].

CHOMYN, A ;

MARTINUZZI, A ;

YONEDA, M ;

DAGA, A ;

HURKO, O ;

JOHNS, D ;

LAI, ST ;

NONAKA, I ;

ANGELINI, C ;

ATTARDI, G .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) :4221-4225

[7] Mitochondrial DNA mutations in human disease [J].

Dimauro, S ;

Schon, EA .

AMERICAN JOURNAL OF MEDICAL GENETICS, 2001, 106 (01) :18-26

[8] Pathogenic Mitochondrial tRNA Mutations - Which Mutations Are Inherited and Why? [J].

Elson, Joanna L. ;

Swalwell, Helen ;

Blakely, Emma L. ;

McFarland, Robert ;

Taylor, Robert W. ;

Turnbull, Doug M. .

HUMAN MUTATION, 2009, 30 (11) :E984-E992

[9] A MUTATION IN THE TRANSFER RNALEU(UUR) GENE ASSOCIATED WITH THE MELAS SUBGROUP OF MITOCHONDRIAL ENCEPHALOMYOPATHIES [J].

GOTO, Y ;

NONAKA, I ;

HORAI, S .

NATURE, 1990, 348 (6302) :651-653

[10] Progressive cerebral vascular degeneration with mitochondrial encephalopathy [J].

Longo, Nicola ;

Schrijver, Iris ;

Vogel, Hannes ;

Pique, Lynn M. ;

Cowan, Tina M. ;

Pasquali, Marzia ;

Steinberg, Gary K. ;

Hedlund, Gary L. ;

Ernst, Sharon L. ;

Gallagher, Renata C. ;

Enns, Gregory M. .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2008, 146A (03) :361-367

← 1 2 3 →

The pathogenic m.3243A&gt;T mitochondrial DNA mutation is associated with a variable neurological phenotype

The pathogenic m.3243A>T mitochondrial DNA mutation is associated with a variable neurological phenotype