Mutation Analysis in 16 Patients With mtDNA Depletion

被引：58

作者：

Carrozzo, R. ^{[1
]}

Bornstein, B. ^{[2
]}

Lucioli, S. ^{[1
]}

Campos, Y. ^{[3
]}

de la Pena, P. ^{[2
]}

Petit, N. ^{[2
]}

Dionisi-Vici, C. ^{[1
]}

Vilarinho, L. ^{[4
]}

Rizza, T. ^{[1
]}

Bertini, E. ^{[1
]}

Garesse, R. ^{[2
]}

Santorelli, F. M. ^{[1
,5
]}

Arenas, J. ^{[3
]}

机构：

[1] Childrens Hosp Bambino Gesu, Mol Med Unit, Piazza S Onofrio 4, I-00165 Rome, Italy

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

[3] Hosp 12 Octubre, Ctr Invest, Madrid, Spain

[4] Inst Genet Med Jacinto Magalhaes, Dept Biol Clin, Porto, Portugal

[5] Univ Roma La Sapienza, Dept Clin Neurol & ORL, Rome, Italy

来源：

HUMAN MUTATION | 2003年 / 21卷 / 04期

关键词：

mitochondrial DNA depletion syndrome; MDS; TK2; DGUOK; SLC25A19; DNC; NT5M; d-NT2; mutation screening;

D O I：

10.1002/humu.9135

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Sixteen unrelated Southern European patients with the mitochondrial depletion syndrome (MDS) were analyzed for mutations in the TK2 and DGUOK genes. Three novel mutations were identified in TK2 (R183G, R254X, and 142insG). When we analyzed additional genes involved in the dNTPs pool, such as SLC25A19 (DNC) and NT5M (d-NT2), we did not detect mutations. The current study suggest that scanning the TK2, DGUOK, SLC25A19, and NT5M genes is likely to help about 10% of MDS families in terms of genetic counseling. Also, our findings indicate that genotype-phenotype correlations are not straightforward in MDS. (c) 2003 Wiley-Liss, Inc.

引用

页码：453 / 454

页数：7

共 16 条

[1]

Antonarakis SE, 1998, HUM MUTAT, V11, P1

[2] Characterization of a dCTP transport activity reconstituted from human mitochondria [J].

Bridges, EG ;

Jiang, ZL ;

Cheng, YC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (08) :4620-4625

[3] Clinical heterogeneity associated with mitochondrial DNA depletion in muscle [J].

Campos, Y ;

Martín, MA ;

García-Silva, T ;

del Hoyo, P ;

Rubio, JC ;

Castro-Gago, M ;

García-Peñas, J ;

Casas, J ;

Cabello, A ;

Ricoy, JR ;

Arenas, J .

NEUROMUSCULAR DISORDERS, 1998, 8 (08) :568-573

[4] The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals [J].

Dolce, V ;

Fiermonte, G ;

Runswick, MJ ;

Palmieri, F ;

Walker, JE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) :2284-2288

[5] Depletion of the other genome-mitochondrial DNA depletion syndromes in humans [J].

Elpeleg, O ;

Mandel, H ;

Saada, A .

JOURNAL OF MOLECULAR MEDICINE-JMM, 2002, 80 (07) :389-396

[6] Defects of intergenomic communication:: autosomal disorders that cause multiple deletions and depletion of mitochondrial DNA [J].

Hirano, M ;

Marti, R ;

Ferreiro-Barros, C ;

Vilà, MR ;

Tadesse, S ;

Nishigaki, Y ;

Nishino, I ;

Vu, TH .

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2001, 12 (06) :417-427

[7] Mitochondrial DNA depletion -: Mutations in thymidine kinase gene with myopathy and SMA [J].

Mancuso, M ;

Salviati, L ;

Sacconi, S ;

Otaegui, D ;

Camaño, P ;

Marina, A ;

Bacman, S ;

Moraes, CT ;

Carlo, JR ;

Garcia, M ;

Garcia-Alvarez, M ;

Monzon, L ;

Naini, AB ;

Hirano, M ;

Bonilla, E ;

Taratuto, AL ;

DiMauro, S ;

Vu, TH .

NEUROLOGY, 2002, 59 (08) :1197-1202

[8] The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA [J].

Mandel, H ;

Szargel, R ;

Labay, V ;

Elpeleg, O ;

Saada, A ;

Shalata, A ;

Anbinder, Y ;

Berkowitz, D ;

Hartman, C ;

Barak, M ;

Eriksson, S ;

Cohen, N .

NATURE GENETICS, 2001, 29 (03) :337-341

[9]

MORAES CT, 1991, AM J HUM GENET, V48, P492

[10] Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder [J].

Nishino, I ;

Spinazzola, A ;

Hirano, M .

SCIENCE, 1999, 283 (5402) :689-692

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