Hearing Loss in a Patient With the Myopathic Form of Mitochondrial DNA Depletion Syndrome and a Novel Mutation in the TK2 Gene

被引：0

作者：

Marti, Ramon ^{[1
,5
]}

Nascimento, Andres ^{[2
,5
]}

Colomer, Jaume ^{[2
,5
]}

Lara, Mari C. ^{[1
,5
]}

Lopez-Gallardo, Ester ^{[3
,5
]}

Ruiz-Pesini, Eduardo ^{[3
,5
]}

Montoya, Julio ^{[3
,5
]}

Andreu, Antoni L. ^{[1
,5
]}

Briones, Paz ^{[4
,5
]}

Pineda, Merce ^{[2
,5
]}

机构：

[1] Hosp Univ Hebron, Inst Recerca, Lab Mitochondria Disorders, Barcelona 08035, Spain

[2] Hosp St Joan de Deu, Dept Neuropediat & Biochem, Barcelona 08950, Spain

[3] Univ Zaragoza, Dept Bioquim & Biol Mol & Celular, E-50013 Zaragoza, Spain

[4] Hosp Clin Barcelona, Inst Bioquim Clin, Serv Bioquim & Genet Mol, Barcelona 08028, Spain

[5] ISCIII, Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain

来源：

PEDIATRIC RESEARCH | 2010年 / 68卷 / 02期

关键词：

THYMIDINE KINASE; MTDNA DEPLETION; DEFICIENCY; RRM2B;

D O I：

10.1203/PDR.0b013e3181e33bbe

中图分类号：

R72 [儿科学];

学科分类号：

100202 ;

摘要：

Mitochondrial DNA (mtDNA) depletion syndrome (MDS) is a devastating disorder of infancy caused by a significant reduction of the number of copies of mitochondrial DNA in one or more tissues. We report a Spanish patient with the myopathic form of MDS, harboring two mutations in the thymidine kinase 2 gene (TK2): a previously reported deletion (p.K244del) and a novel nucleotide duplication in the exon 2, generating a frameshift and premature stop codon. Sensorineural hearing loss was a predominant symptom in the patient and a novel feature of MDS due to TK2 mutations. The patient survived up to the age of 8.5 y, which confirms that survival above the age of 5 y is not infrequent in patients with MDS due to TK2 deficiency. (Pediatr Res 68: 151-154, 2010)

引用

页码：151 / 154

页数：4

共 21 条

[1] Depletion of mtDNA: Syndromes and genes [J].

Alberio, Simona ;

Mineri, Rossana ;

Tiranti, Valeria ;

Zeviani, Massimo .

MITOCHONDRION, 2007, 7 (1-2) :6-12

[2] Mitochondrial non-syndromic sensorineural hearing loss: a clinical, audiological and pathological study from Italy, and revision of the literature [J].

Berrettini, Stefano ;

Forli, Francesca ;

Passetti, Susanna ;

Rocchi, Anna ;

Pollina, Luca ;

Cecchetti, Denise ;

Mancuso, Michelangelo ;

Siciliano, Gabriele .

BIOSCIENCE REPORTS, 2008, 28 (01) :49-59

[3] 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

[4] Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene [J].

Bornstein, Belen ;

Area, Estela ;

Flanigan, Kevin M. ;

Ganesh, Jaya ;

Jayakar, Parul ;

Swoboda, Kathryn J. ;

Coku, Jorida ;

Naini, Ali ;

Shanske, Sara ;

Tanji, Kurenal ;

Hirano, Michio ;

DiMauro, Salvatore .

NEUROMUSCULAR DISORDERS, 2008, 18 (06) :453-459

[5] Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion [J].

Bourdon, Alice ;

Minai, Limor ;

Serre, Valerie ;

Jais, Jean-Philippe ;

Sarzi, Emmanuelle ;

Aubert, Sophie ;

Chretien, Dominique ;

de Lonlay, Pascale ;

Paquis-Flucklinger, Veronique ;

Arakawa, Hirofumi ;

Nakamura, Yusuke ;

Munnich, Arnold ;

Rotig, Agnes .

NATURE GENETICS, 2007, 39 (06) :776-780

[6] Mutation Analysis in 16 Patients With mtDNA Depletion [J].

Carrozzo, R. ;

Bornstein, B. ;

Lucioli, S. ;

Campos, Y. ;

de la Pena, P. ;

Petit, N. ;

Dionisi-Vici, C. ;

Vilarinho, L. ;

Rizza, T. ;

Bertini, E. ;

Garesse, R. ;

Santorelli, F. M. ;

Arenas, J. .

HUMAN MUTATION, 2003, 21 (04) :453-454

[7] Progressive myofiber loss with extensive fibro-fatty replacement in a child with mitochondrial DNA depletion syndrome and novel thymidine kinase 2 gene mutations [J].

Collins, James ;

Bove, Kevin E. ;

Dimmock, David ;

Morehart, Paula ;

Wong, Lee-Jun ;

Wong, Brenda .

NEUROMUSCULAR DISORDERS, 2009, 19 (11) :784-787

[8] Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion [J].

Elpeleg, O ;

Miller, C ;

Hershkovitz, E ;

Bitner-Glindzicz, M ;

Bondi-Rubenstein, G ;

Rahman, S ;

Pagnamenta, A ;

Eshhar, S ;

Saada, A .

AMERICAN JOURNAL OF HUMAN GENETICS, 2005, 76 (06) :1081-1086

[9]

Fischel-Ghodsian N, 1999, HUM MUTAT, V13, P261, DOI 10.1002/(SICI)1098-1004(1999)13:4<261::AID-HUMU1>3.0.CO

[10]

2-W

← 1 2 3 →