Next-generation sequencing of Tunisian Leigh syndrome patients reveals novel variations: impact for diagnosis and treatment.
Biotin
/ genetics
Child
DNA, Mitochondrial
/ genetics
High-Throughput Nucleotide Sequencing
Humans
Leigh Disease
/ diagnosis
Membrane Transport Proteins
/ genetics
Mitochondrial Membrane Transport Proteins
Mitochondrial Proteins
/ genetics
Mutation
Nucleocytoplasmic Transport Proteins
/ genetics
Thiamine
Leigh syndrome
NGS
North Africa
Tunisia
mitochondrial cytopathies
Journal
Bioscience reports
ISSN: 1573-4935
Titre abrégé: Biosci Rep
Pays: England
ID NLM: 8102797
Informations de publication
Date de publication:
30 09 2022
30 09 2022
Historique:
received:
29
01
2022
revised:
22
07
2022
accepted:
23
08
2022
pubmed:
13
9
2022
medline:
24
9
2022
entrez:
12
9
2022
Statut:
ppublish
Résumé
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 the present 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. Bioinformatic 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.
Identifiants
pubmed: 36093993
pii: 231779
doi: 10.1042/BSR20220194
pmc: PMC9508526
pii:
doi:
Substances chimiques
DNA, Mitochondrial
0
ETHE1 protein, human
0
Membrane Transport Proteins
0
Mitochondrial Membrane Transport Proteins
0
Mitochondrial Proteins
0
Nucleocytoplasmic Transport Proteins
0
SLC19A3 protein, human
0
SLC25A19 protein, human
0
Biotin
6SO6U10H04
Thiamine
X66NSO3N35
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022 The Author(s).
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