Next generation sequencing of Tunisian Leigh syndrome patients reveals novel variations: impact for diagnosis and treatment - Institut Pasteur de Tunis Access content directly
Journal Articles Bioscience Reports Year : 2022

Next generation sequencing of Tunisian Leigh syndrome patients reveals novel variations: impact for diagnosis and treatment

Cyrine Drissi
  • Function : Author
Saïd Galaï
  • Function : Author

Abstract

Mitochondrial cytopathies, among which the Leigh syndrome (LS), are caused by variants either in the mitochondrial or the nuclear genome, affecting the oxidative phosphorylation process. The aim of this study consisted in defining the molecular diagnosis of a group of Tunisian patients with LS. Six children, belonging to five Tunisian families, with clinical and imaging presentations suggestive of LS were recruited. Whole mitochondrial DNA and targeted next generation sequencing of a panel of 281 nuclear genes involved in mitochondrial physiology were performed. Bio-informatic analyses were achieved in order to identify deleterious variations. A single m.10197G>A (p.Ala47Thr) variant was found in the mitochondrial MT-ND3 gene in one patient, while the others were related to autosomal homozygous variants: two c.1412delA (p.Gln471ArgfsTer42) and c.1264A>G (p.Thr422Ala) in SLC19A3, one c.454C>G (p.Pro152Ala) in SLC25A19 and one c.122G>A (p.Gly41Asp) in ETHE1. Our findings demonstrate the usefulness of genomic investigations to improve LS diagnosis in consanguineous populations, and further allow for treating the patients harboring variants in SLC19A3 and SLC25A19 that contribute to thiamine transport, by thiamine and biotin supplementation. Considering the Tunisian genetic background, the newly identified variants could be screened in patients with similar clinical presentation in related populations.
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Dates and versions

hal-03861081 , version 1 (19-11-2022)

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Meriem Hechmi, Majida Charif, Ichraf Kraoua, Meriem Fassatoui, Hamza Dallali, et al.. Next generation sequencing of Tunisian Leigh syndrome patients reveals novel variations: impact for diagnosis and treatment. Bioscience Reports, 2022, 42 (9), ⟨10.1042/BSR20220194⟩. ⟨hal-03861081⟩
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