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Two new mutations in the MT-TW gene leading to the disruption of the secondary structure of the tRNA(Trp) in patients with Leigh syndrome

Mkaouar-Rebai, Emna; Chamkha, Imen LU ; Kammoun, Fatma; Kammoun, Thouraya; Aloulou, Hajer; Hachicha, Mongia; Triki, Chahnez and Fakhfakh, Faiza (2009) In Molecular Genetics and Metabolism 97(3). p.84-179
Abstract

Leigh syndrome is a progressive neurodegenerative disorder occurring in infancy and childhood characterized in most cases by a psychomotor retardation, optic atrophy, ataxia, dystonia, failure to thrive, seizures and respiratory failure. In this study, we performed a systematic sequence analysis of mitochondrial genes associated with LS in Tunisian patients. We sequenced the encoded complex I units: ND2, ND3, ND4, ND5 and ND6 genes and the mitochondrial ATPase 6, tRNA(Val), tRNA(Leu(UUR)), tRNA(Trp) and tRNA(Lys) genes in 10 unrelated patients with Leigh syndrome. We revealed the presence of 34 reported polymorphisms, nine novel nucleotide variants and two new mutations (T5523G and A5559G) in the tested patients. These two mutations... (More)

Leigh syndrome is a progressive neurodegenerative disorder occurring in infancy and childhood characterized in most cases by a psychomotor retardation, optic atrophy, ataxia, dystonia, failure to thrive, seizures and respiratory failure. In this study, we performed a systematic sequence analysis of mitochondrial genes associated with LS in Tunisian patients. We sequenced the encoded complex I units: ND2, ND3, ND4, ND5 and ND6 genes and the mitochondrial ATPase 6, tRNA(Val), tRNA(Leu(UUR)), tRNA(Trp) and tRNA(Lys) genes in 10 unrelated patients with Leigh syndrome. We revealed the presence of 34 reported polymorphisms, nine novel nucleotide variants and two new mutations (T5523G and A5559G) in the tested patients. These two mutations were localized in two conserved regions of the tRNA(Trp) and affect, respectively, the D-stem and the T-stem of the mitochondrial tRNA leading to a disruption of the secondary structure of this tRNA. SSP-PCR analysis showed that the T5523G and A5559G mutations were present with respective heteroplasmic rates of 66% and 43 %. We report here the first mutational screening of mitochondrial mutations in Tunisian patients with Leigh syndrome which described two novel mutations associated with this disorder.

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publishing date
type
Contribution to journal
publication status
published
keywords
Adolescent, Adult, Asian Continental Ancestry Group, Base Sequence, Child, Child, Preschool, DNA Mutational Analysis, Female, Humans, Leigh Disease, Male, Mitochondria, Molecular Sequence Data, Mutation, Nucleic Acid Conformation, RNA, Transfer, Trp, Sequence Alignment, Tunisia
in
Molecular Genetics and Metabolism
volume
97
issue
3
pages
6 pages
publisher
Elsevier
external identifiers
  • Scopus:67349264539
ISSN
1096-7192
DOI
10.1016/j.ymgme.2009.03.003
language
English
LU publication?
no
id
e0a14610-f9c6-4346-b2db-88993fcc9ddb
date added to LUP
2016-09-14 13:46:08
date last changed
2017-01-01 08:33:51
@article{e0a14610-f9c6-4346-b2db-88993fcc9ddb,
  abstract     = {<p>Leigh syndrome is a progressive neurodegenerative disorder occurring in infancy and childhood characterized in most cases by a psychomotor retardation, optic atrophy, ataxia, dystonia, failure to thrive, seizures and respiratory failure. In this study, we performed a systematic sequence analysis of mitochondrial genes associated with LS in Tunisian patients. We sequenced the encoded complex I units: ND2, ND3, ND4, ND5 and ND6 genes and the mitochondrial ATPase 6, tRNA(Val), tRNA(Leu(UUR)), tRNA(Trp) and tRNA(Lys) genes in 10 unrelated patients with Leigh syndrome. We revealed the presence of 34 reported polymorphisms, nine novel nucleotide variants and two new mutations (T5523G and A5559G) in the tested patients. These two mutations were localized in two conserved regions of the tRNA(Trp) and affect, respectively, the D-stem and the T-stem of the mitochondrial tRNA leading to a disruption of the secondary structure of this tRNA. SSP-PCR analysis showed that the T5523G and A5559G mutations were present with respective heteroplasmic rates of 66% and 43 %. We report here the first mutational screening of mitochondrial mutations in Tunisian patients with Leigh syndrome which described two novel mutations associated with this disorder.</p>},
  author       = {Mkaouar-Rebai, Emna and Chamkha, Imen and Kammoun, Fatma and Kammoun, Thouraya and Aloulou, Hajer and Hachicha, Mongia and Triki, Chahnez and Fakhfakh, Faiza},
  issn         = {1096-7192},
  keyword      = {Adolescent,Adult,Asian Continental Ancestry Group,Base Sequence,Child,Child, Preschool,DNA Mutational Analysis,Female,Humans,Leigh Disease,Male,Mitochondria,Molecular Sequence Data,Mutation,Nucleic Acid Conformation,RNA, Transfer, Trp,Sequence Alignment,Tunisia},
  language     = {eng},
  number       = {3},
  pages        = {84--179},
  publisher    = {Elsevier},
  series       = {Molecular Genetics and Metabolism},
  title        = {Two new mutations in the MT-TW gene leading to the disruption of the secondary structure of the tRNA(Trp) in patients with Leigh syndrome},
  url          = {http://dx.doi.org/10.1016/j.ymgme.2009.03.003},
  volume       = {97},
  year         = {2009},
}