Early-onset multisystem mitochondrial disorder caused by a nonsense mutation in the mitochondrial DNA cytochrome c oxidase II gene

被引：45

作者：

Campos, Y

García-Redondo, A

Fernández-Moreno, MA

Martínez-Pardo, M

Goda, G

Rubio, JC

Martín, MA

del Hoyo, P

Cabello, A

Bornstein, B

Garesse, R

Arenas, J

机构：

[1] Univ Hosp, Ctr Invest, Madrid, Spain

[2] Univ Hosp, Dept Neuropatol, Madrid, Spain

[3] UAM, CSIC, Inst Invest Biomed Alberto Sols, Madrid, Spain

[4] Hosp Univ Ramon y Cajal, Dept Pediat, Madrid, Spain

来源：

ANNALS OF NEUROLOGY | 2001年 / 50卷 / 03期

关键词：

D O I：

10.1002/ana.1141

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

We report the first nonsense mutation (G7896A) in the mtDNA gene for subunit Il of cytochrome c oxidase (COX in a patient with early-onset multisystem disease and COX deficiency in muscle. The mutation was heteroplasmic in muscle, blood, and fibroblasts from the patient and abundantly present in COX-deficient fibers, but less abundant in COX-positive fibers; it was not found in blood samples from the patient's asymptomatic maternal relatives. Immunoblot analysis showed a reduced concentration of both COX II and COX I polypeptides, suggesting impaired assembly of COX holoenzyme.

引用

页码：409 / 413

页数：5

共 20 条

[1] SEQUENCE AND ORGANIZATION OF THE HUMAN MITOCHONDRIAL GENOME [J].

ANDERSON, S ;

BANKIER, AT ;

BARRELL, BG ;

DEBRUIJN, MHL ;

COULSON, AR ;

DROUIN, J ;

EPERON, IC ;

NIERLICH, DP ;

ROE, BA ;

SANGER, F ;

SCHREIER, PH ;

SMITH, AJH ;

STADEN, R ;

YOUNG, IG .

NATURE, 1981, 290 (5806) :457-465

[2] A stop-codon mutation in the human mtDNA cytochrome c oxidase I gene disrupts the functional structure of complex IV [J].

Bruno, C ;

Martinuzzi, A ;

Tang, YY ;

Andreu, AL ;

Pallotti, F ;

Bonilla, E ;

Shanske, S ;

Fu, J ;

Sue, CM ;

Angelini, C ;

DiMauro, S ;

Manfredi, G .

AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 65 (03) :611-620

[3] An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II gene results in lower levels of the protein and a mitochondrial encephalomyopathy [J].

Clark, KM ;

Taylor, RW ;

Johnson, MA ;

Chinnery, PF ;

Chrzanowska-Lightowlers, ZMA ;

Andrews, RM ;

Nelson, IP ;

Wood, NW ;

Lamont, PJ ;

Hanna, MG ;

Lightowlers, RN ;

Turnbull, DM .

AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 64 (05) :1330-1339

[4] Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease [J].

Comi, GP ;

Bordoni, A ;

Salani, S ;

Franceschina, L ;

Sciacco, M ;

Prelle, A ;

Fortunato, F ;

Zeviani, M ;

Napoli, L ;

Bresolin, N ;

Moggio, M ;

Ausenda, CD ;

Taanman, JW ;

Scarlato, G .

ANNALS OF NEUROLOGY, 1998, 43 (01) :110-116

[5]

Dickinson EK, 2000, J BIOL CHEM, V275, P26780

[6] Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia [J].

Gattermann, N ;

Retzlaff, S ;

Wang, YL ;

Hofhaus, G ;

Heinisch, J ;

Aul, C ;

Schneider, W .

BLOOD, 1997, 90 (12) :4961-4972

[7] Cytochrome c oxidase deficiency associated with the first stop-codon point mutation in human mtDNA [J].

Hanna, MG ;

Nelson, IP ;

Rahman, S ;

Lane, RJM ;

Land, J ;

Heales, S ;

Cooper, MJ ;

Schapira, AHV ;

Morgan-Hughes, JA ;

Wood, NW .

AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 63 (01) :29-36

[8] Mutations in SCO2 are associated with a distinct form of hypertrophic cardiomyopathy and cytochrome c oxidase deficiency [J].

Jaksch, M ;

Ogilvie, I ;

Yao, JB ;

Kortenhaus, G ;

Bresser, HG ;

Gerbitz, KD ;

Shoubridge, EA .

HUMAN MOLECULAR GENETICS, 2000, 9 (05) :795-801

[9] Recurrent myoglobinuria due to a nonsense mutation in the COX I gene of mitochondrial DNA [J].

Karadimas, CL ;

Greenstein, P ;

Sue, CM ;

Joseph, JT ;

Tanji, K ;

Haller, RG ;

Taivassalo, T ;

Davidson, MM ;

Shanske, S ;

Bonilla, E ;

DiMauro, S .

NEUROLOGY, 2000, 55 (05) :644-649

[10] A microdeletion in cytochrome c oxidase (COX) subunit III associated with COX deficiency and recurrent myoglobinuria [J].

Keightley, JA ;

Hoffbuhr, KC ;

Burton, MD ;

Salas, VM ;

Johnston, WSW ;

Penn, AMW ;

Buist, NRM ;

Kennaway, NG .

NATURE GENETICS, 1996, 12 (04) :410-416

← 1 2 →