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.
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.
Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Avenue Magida Boulila, 3029 Sfax, Tunisia. emna_mkaouar@mail2world.com
Emna
E
Mkaouar-Rebai
Imen
I
Chamkha
Fatma
F
Kammoun
Thouraya
T
Kammoun
Hajer
H
Aloulou
Mongia
M
Hachicha
Chahnez
C
Triki
Faiza
F
Fakhfakh
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007888:Leigh Disease / Q000235:genetics*; D008297:Male; D008928:Mitochondria / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009690:Nucleic Acid Conformation; D012364:RNA, Transfer, Trp / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D014416:Tunisia
D012364:RNA, Transfer, Trp