Leigh syndrome is a genetically heterogeneous, neurodegenerative disorder that predominantly affects children and leads to death within months or years. Mutations causing this disease have been found in both mitochondrial and nuclear DNA. The present report describes a Tunisian family with a maternally inherited Leigh syndrome harboring the mitochondrial T8993G mutation in the ATPase 6 gene. Polymerase chain reaction-restriction fragment length polymorphism analysis with the MspI restriction endonuclease, quantified with a digital image analyzer and gel documentation system, showed that the T8993G mutation was present with a high percentage in the blood of the three patients tested. This mutation was also detected in the asymptomatic mothers of these three patients (90, 96, and 60%). Two novel mitochondrial mutations were identified in the mitochondrial ATP6 gene -- T8741G (L72R) and A8795G (H90R) -- and three novel polymorphisms. Altogether, Leigh syndrome presenting the T8993G mutation in the ATPase 6 gene with variable heteroplasmic loads (44-98%) in a single Tunisian family is a novel finding.
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http://dx.doi.org/10.1016/j.pediatrneurol.2009.01.004 | DOI Listing |
Exp Neurol
December 2024
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, United States of America; Department of Neurological Surgery, University of Washington School of Medicine, Seattle, WA 98108, USA. Electronic address:
Swallowing, both nutritive and non-nutritive, is highly dysfunctional in children with Leigh Syndrome (LS) and contributes to the need for both gastrostomy and tracheostomy tube placement. Without these interventions aspiration of food, liquid, and mucus occur resulting in repeated bouts of respiratory infection. No study has investigated whether mouse models of LS, a neurometabolic disorder, exhibit dysfunctions in neuromuscular activity of swallow and breathing integration.
View Article and Find Full Text PDFNeurotherapeutics
December 2024
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Neurocritical Care Division, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, MD, United States; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address:
Brain ischemia is a major cause of neurological dysfunction and mortality worldwide. It occurs not only acutely, such as in acute ischemic stroke (AIS), but also in chronic conditions like cerebral small vessel disease (cSVD). Any other conditions resulting in brain hypoperfusion can also lead to ischemia.
View Article and Find Full Text PDFActa Pharmacol Sin
December 2024
Laboratory of Biochemistry, Structural and Molecular Biology, Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125, Bari, Italy.
Carnitine O-acetyltransferase (CRAT) is a crucial enzyme involved in mitochondrial energy metabolism. Alterations in CRAT activity have emerged as significant contributors to the pathogenesis of Leigh syndrome and related mitochondrial disorders. In this study we employed an integrated approach combining in silico docking analysis and virtual screening of chemical libraries with subsequent in vitro validation to identify small molecule modulators of the activity of the wild type (WT) CRAT and the p.
View Article and Find Full Text PDFParkinsonism Relat Disord
December 2024
Division of General Neurology and Ataxia Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Sao Paulo, SP, Brazil.
Genet Med Open
February 2024
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Central Parkway, Newcastle upon Tyne, United Kingdom.
Purpose: In parent-child trios with genome sequencing data, we investigated inherited biallelic deletions to identify known and novel genetic disorders.
Methods: We developed a copy-number variations analysis pipeline based on autosomal genome sequencing read depth of Genomics England 100,000 Genomes Project data from 11,754 parent-child trios and additional 18,875 non-trios. A control cohort of 15,440 cancer patients provided independent deletion frequencies.
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